Variant Annotation
Available parameters and response documentation is available here
GET /lookup/chr11-117222650-A-?add-ACMG-annotation=1&add-source-databases=bravo%2Cisb_kaviar3&format=api
{
"chromosome": "chr11",
"alt": "",
"ref": "A",
"pos": 117222650,
"variant_id": "10190111172226509001",
"regions": {
"uniprot_regions": {
"version": "08-Dec-2023",
"items": [
{
"absolute_positon": 501983937,
"amino_acid": "M1-E28,E28-C65,C65-L131,A132-L184,P185-Q229,S230-E255,E256-Q384,E385-L411,D412-Q439,A440-R470,R470-R526,R526-V575,V575-S645,S645-R689,R689-E761,A762-E787,V788-E831,L832-E872,E873-Q920,E921-Q948,E949-E971,E972-S1030,S1030-T1072,N1073-S1093,S1093-K1167...",
"chromo": "chr11",
"colour": "255,0,0",
"description": null,
"length": 85413,
"position": 117198570,
"protein": "CE164_HUMAN",
"type": "homo_sapiens proteome sequences",
"pub_med_references": null
},
{
"absolute_positon": 501994670,
"amino_acid": "M1-Y194",
"chromo": "chr11",
"colour": "255,102,0",
"description": "Interaction with ATRIP",
"length": 23847,
"position": 117209303,
"protein": "CE164_HUMAN",
"type": "region of interest",
"pub_med_references": null
},
{
"absolute_positon": 502007997,
"amino_acid": "G107-S135",
"chromo": "chr11",
"colour": "255,102,0",
"description": "Disordered",
"length": 9933,
"position": 117222630,
"protein": "CE164_HUMAN",
"type": "region of interest",
"pub_med_references": null
}
]
}
},
"variant_type": "Deletion (homopolymer)",
"cytobands": "11q23.3",
"refseq_transcripts": [
{
"items": [
{
"name": "NM_014956.5",
"strand": "+",
"coding_impact": "frameshift",
"function": [
"NMD",
"coding"
],
"hgvs": "c.347del",
"hgvs_p1": "K116Rfs*22",
"hgvs_p3": "p.(Lys116ArgfsTer22)",
"location": "exon 5 of 33 position 153 of 199",
"coding_location": "116 of 1461",
"canonical": true,
"gene_symbol": "CEP164",
"splice_distance": "-47",
"ensembl_support_level": null,
"ensembl_appris": null,
"mane_select": "ENST00000278935.8",
"mane_plus": null,
"uniprot_id": null
},
{
"name": "NM_001271933.2",
"strand": "+",
"coding_impact": "frameshift",
"function": [
"NMD",
"coding"
],
"hgvs": "c.347del",
"hgvs_p1": "K116Rfs*22",
"hgvs_p3": "p.(Lys116ArgfsTer22)",
"location": "exon 4 of 32 position 153 of 199",
"coding_location": "116 of 1456",
"canonical": false,
"gene_symbol": "CEP164",
"splice_distance": "-47",
"ensembl_support_level": null,
"ensembl_appris": null,
"mane_select": null,
"mane_plus": null,
"uniprot_id": null
}
],
"version": "223"
}
],
"ensembl_transcripts": [
{
"items": [
{
"name": "ENST00000278935.3",
"strand": "+",
"coding_impact": "frameshift",
"function": [
"NMD",
"coding"
],
"hgvs": "c.347del",
"hgvs_p1": "K116Rfs*22",
"hgvs_p3": "p.(Lys116ArgfsTer22)",
"location": "exon 5 of 33 position 153 of 199",
"coding_location": "116 of 1461",
"canonical": true,
"gene_symbol": "CEP164",
"splice_distance": "-47",
"ensembl_support_level": "1",
"ensembl_appris": "principal1",
"mane_select": "NM_014956.5",
"mane_plus": null,
"uniprot_id": "Q9UPV0"
},
{
"name": "ENST00000525416.1",
"strand": "+",
"coding_impact": "frameshift",
"function": [
"coding"
],
"hgvs": "c.209del",
"hgvs_p1": "K70Rfs*22",
"hgvs_p3": "p.(Lys70ArgfsTer22)",
"location": "exon 4 of 5 position 153 of 199",
"coding_location": "70 of 122",
"canonical": false,
"gene_symbol": "CEP164",
"splice_distance": "-47",
"ensembl_support_level": "3",
"ensembl_appris": null,
"mane_select": null,
"mane_plus": null,
"uniprot_id": null
},
{
"name": "ENST00000525734.1",
"strand": "+",
"coding_impact": null,
"function": [
"3'utr"
],
"hgvs": "c.*2del",
"hgvs_p1": "p.?",
"hgvs_p3": "p.?",
"location": "exon 5 of 5 (3'UTR) position 153 of 153",
"coding_location": null,
"canonical": false,
"gene_symbol": "CEP164",
"splice_distance": "153",
"ensembl_support_level": "2",
"ensembl_appris": null,
"mane_select": null,
"mane_plus": null,
"uniprot_id": null
},
{
"name": "ENST00000527609.1",
"strand": "+",
"coding_impact": "frameshift",
"function": [
"coding"
],
"hgvs": "c.347del",
"hgvs_p1": "K116Rfs",
"hgvs_p3": "p.(Lys116Argfs)",
"location": "exon 5 of 5 position 153 of 170",
"coding_location": "116 of 121",
"canonical": false,
"gene_symbol": "CEP164",
"splice_distance": "153",
"ensembl_support_level": "1",
"ensembl_appris": null,
"mane_select": null,
"mane_plus": null,
"uniprot_id": null
},
{
"name": "ENST00000533153.1",
"strand": "+",
"coding_impact": "frameshift",
"function": [
"NMD",
"coding"
],
"hgvs": "c.209del",
"hgvs_p1": "K70Rfs*22",
"hgvs_p3": "p.(Lys70ArgfsTer22)",
"location": "exon 3 of 5 position 153 of 199",
"coding_location": "70 of 158",
"canonical": false,
"gene_symbol": "CEP164",
"splice_distance": "-47",
"ensembl_support_level": "3",
"ensembl_appris": null,
"mane_select": null,
"mane_plus": null,
"uniprot_id": null
},
{
"name": "ENST00000533570.1",
"strand": "+",
"coding_impact": "frameshift",
"function": [
"coding"
],
"hgvs": "c.347del",
"hgvs_p1": "K116Rfs",
"hgvs_p3": "p.(Lys116Argfs)",
"location": "exon 4 of 4 position 153 of 171",
"coding_location": "116 of 121",
"canonical": false,
"gene_symbol": "CEP164",
"splice_distance": "153",
"ensembl_support_level": "1",
"ensembl_appris": null,
"mane_select": null,
"mane_plus": null,
"uniprot_id": null
}
],
"version": "111"
}
],
"gnomad_exomes": [
{
"version": "2.1.1",
"filter": "PASS",
"ac": 5026,
"an": 78708,
"af": 0.06385627890430452,
"ac_afr": 311,
"ac_amr": 637,
"ac_asj": 145,
"ac_eas": 303,
"ac_eas_kor": 50,
"ac_eas_jpn": 2,
"ac_eas_oea": 251,
"ac_fin": 472,
"ac_nfe": 2514,
"ac_nfe_bgr": 55,
"ac_nfe_est": 8,
"ac_nfe_nwe": 621,
"ac_nfe_onf": 718,
"ac_nfe_seu": 405,
"ac_nfe_swe": 707,
"ac_oth": 122,
"ac_sas": 522,
"ac_afr_male": 126,
"ac_amr_male": 236,
"ac_asj_male": 78,
"ac_eas_male": 159,
"ac_fin_male": 247,
"ac_nfe_male": 1479,
"ac_oth_male": 61,
"ac_sas_male": 413,
"ac_afr_female": 185,
"ac_amr_female": 401,
"ac_asj_female": 67,
"ac_eas_female": 144,
"ac_fin_female": 225,
"ac_nfe_female": 1035,
"ac_oth_female": 61,
"ac_sas_female": 109,
"ac_male": 2799,
"ac_female": 2227,
"an_afr": 5350,
"an_amr": 10222,
"an_asj": 3288,
"an_eas": 5416,
"an_eas_kor": 1120,
"an_eas_jpn": 78,
"an_eas_oea": 4218,
"an_fin": 7278,
"an_nfe": 36394,
"an_nfe_bgr": 966,
"an_nfe_est": 92,
"an_nfe_nwe": 13648,
"an_nfe_onf": 10148,
"an_nfe_seu": 3530,
"an_nfe_swe": 8010,
"an_oth": 1910,
"an_sas": 8850,
"an_afr_male": 1976,
"an_amr_male": 4330,
"an_asj_male": 1780,
"an_eas_male": 2692,
"an_fin_male": 3844,
"an_nfe_male": 20242,
"an_oth_male": 988,
"an_sas_male": 6606,
"an_afr_female": 3374,
"an_amr_female": 5892,
"an_asj_female": 1508,
"an_eas_female": 2724,
"an_fin_female": 3434,
"an_nfe_female": 16152,
"an_oth_female": 922,
"an_sas_female": 2244,
"an_male": 42458,
"an_female": 36250,
"age_hist_het_under_30": 119,
"age_hist_het_30_35": 140,
"age_hist_het_35_40": 213,
"age_hist_het_40_45": 443,
"age_hist_het_45_50": 462,
"age_hist_het_50_55": 522,
"age_hist_het_55_60": 532,
"age_hist_het_60_65": 450,
"age_hist_het_65_70": 427,
"age_hist_het_70_75": 309,
"age_hist_het_75_80": 247,
"age_hist_het_over_80": 101,
"variant_type": "mixed",
"lcr": true,
"original_variant": "11-117222647-GA-G",
"main_data": "ƒ = 0.0639"
}
],
"gnomad_exomes_coverage": [
{
"version": "2.1",
"coverage_mean": [
54.263999938964844
],
"coverage_median": [
42.0
],
"coverage_20_frequency": [
0.9350260933256019
]
}
],
"gnomad_genomes": [
{
"version": "2.1.1",
"filter": "PASS",
"ac": 30,
"an": 23226,
"af": 0.0012916559028674762,
"ac_afr": 4,
"ac_amr": 1,
"ac_eas": 1,
"ac_fin": 11,
"ac_nfe": 12,
"ac_nfe_est": 1,
"ac_nfe_nwe": 8,
"ac_nfe_onf": 2,
"ac_nfe_seu": 1,
"ac_oth": 1,
"ac_afr_male": 3,
"ac_amr_male": 1,
"ac_eas_male": 1,
"ac_fin_male": 6,
"ac_nfe_male": 5,
"ac_oth_male": 1,
"ac_afr_female": 1,
"ac_fin_female": 5,
"ac_nfe_female": 7,
"ac_male": 17,
"ac_female": 13,
"an_afr": 7398,
"an_amr": 544,
"an_asj": 228,
"an_eas": 1456,
"an_fin": 1178,
"an_nfe": 11746,
"an_nfe_est": 2812,
"an_nfe_nwe": 7266,
"an_nfe_onf": 1618,
"an_nfe_seu": 50,
"an_oth": 676,
"an_afr_male": 4276,
"an_amr_male": 260,
"an_asj_male": 172,
"an_eas_male": 968,
"an_fin_male": 550,
"an_nfe_male": 6562,
"an_oth_male": 342,
"an_afr_female": 3122,
"an_amr_female": 284,
"an_asj_female": 56,
"an_eas_female": 488,
"an_fin_female": 628,
"an_nfe_female": 5184,
"an_oth_female": 334,
"an_male": 13130,
"an_female": 10096,
"age_hist_het_under_30": 3,
"age_hist_het_30_35": 3,
"age_hist_het_35_40": 1,
"age_hist_het_40_45": 2,
"age_hist_het_45_50": 1,
"age_hist_het_50_55": 1,
"age_hist_het_55_60": 2,
"age_hist_het_65_70": 1,
"variant_type": "mixed",
"lcr": true,
"original_variant": "11-117222647-GA-G",
"main_data": "ƒ = 0.00129"
}
],
"gnomad_genomes_coverage": [
{
"version": "2.1",
"coverage_mean": [
24.854999542236328
],
"coverage_median": [
25.0
],
"coverage_20_frequency": [
0.7111423078096866
]
}
],
"isb_kaviar3": [
{
"version": "4-Feb-2016",
"ac": [
4,
5,
12734
],
"an": [
155504,
155504,
155504
],
"main_data": null
}
],
"ncbi_clinvar2": [
{
"version": "01-Apr-2024",
"review_status": "criteria provided, multiple submitters, no conflicts",
"review_stars": 2,
"variation_id": 993033,
"num_submitters": 3,
"pub_med_references": null,
"clinical_significance": [
"Benign"
],
"last_evaluation": "20240305",
"origin": null,
"accessions": [
{
"accession_id": "RCV001283852",
"allele_id": 980941,
"review_description": "Benign",
"review_status": "criteria provided, single submitter",
"clinical_significance": [
"Benign"
],
"title": "NM_014956.5(CEP164):c.347del (p.Lys116fs) AND Nephronophthisis 15",
"date_created": 20210126,
"diseases": [
{
"normalized_disease": [
"Nephronophthisis 15"
],
"symbols": {
"orphanet": "3156",
"omim": "614845",
"medgen": "C3541853",
"mondo": "MONDO:0013917"
},
"names": [
"Nephronophthisis 15"
]
}
],
"review_stars": 1,
"review_date": 20231211,
"variation_id": 993033,
"submission_description": [],
"submissions": [
{
"submission_description": [],
"review_description": "Benign",
"submitter_name": "Invitae",
"review_date": 20231211,
"origin": "germline",
"method": "clinical testing",
"submitter_date": 20240207,
"diseases": [
{
"symbols": {
"medgen": "C3541853"
}
}
],
"date_updated": 20240228,
"clinical_significance": [
"Benign"
],
"review_status": "criteria provided, single submitter",
"accession_id": "SCV001727092"
},
{
"submission_description": [],
"review_description": "Likely pathogenic",
"submitter_name": "Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City",
"review_date": 20201011,
"origin": "germline",
"method": "clinical testing",
"submitter_date": 20210113,
"diseases": [
{
"symbols": {
"omim": "614845"
}
}
],
"date_updated": 20210126,
"clinical_significance": [
"Likely pathogenic"
],
"review_status": "no assertion criteria provided",
"accession_id": "SCV001469288"
}
],
"variant_id": 10190111172226509001
},
{
"accession_id": "RCV001797168",
"allele_id": 980941,
"review_description": "Benign",
"review_status": "criteria provided, single submitter",
"clinical_significance": [
"Benign"
],
"title": "NM_014956.5(CEP164):c.347del (p.Lys116fs) AND not provided",
"date_created": 20211224,
"diseases": [
{
"symbols": {
"medgen": "C3661900"
},
"names": [
"Not Provided",
"None Provided"
]
}
],
"review_stars": 1,
"review_date": 20211216,
"variation_id": 993033,
"submission_description": [],
"submissions": [
{
"submission_description": [],
"review_description": "Benign",
"submitter_name": "GeneDx",
"review_date": 20211216,
"origin": "germline",
"method": "clinical testing",
"submitter_date": 20211222,
"diseases": [
{
"names": [
"Not Provided"
]
}
],
"date_updated": 20230304,
"clinical_significance": [
"Benign"
],
"review_status": "criteria provided, single submitter",
"accession_id": "SCV002038650"
}
],
"variant_id": 10190111172226509001
}
],
"main_data": "benign **2**",
"names": [
"NM_014956.5(CEP164):c.347del (p.Lys116fs)"
],
"variant_type": "Deletion"
}
],
"publications": {
"publications": [],
"genes": [
{
"publications": [
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 32367404
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 32055034
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 31248650
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 30847515
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 28125082
},
{
"referenced_by": [
"gene2phenotype",
"GenCC"
],
"pub_med_id": 27708425
},
{
"referenced_by": [
"dbNSFP"
],
"pub_med_id": 23348840
},
{
"referenced_by": [
"gene2phenotype",
"GenCC",
"CGD",
"dbNSFP"
],
"pub_med_id": 22863007
},
{
"referenced_by": [
"dbNSFP"
],
"pub_med_id": 18283122
},
{
"referenced_by": [
"dbNSFP"
],
"pub_med_id": 17954613
}
],
"gene_symbol": "CEP164",
"gene_id": 4000
}
]
},
"bravo": [
{
"version": "Freeze5",
"filter": "PASS",
"ac": 1,
"an": 29118,
"af": null,
"het": 1,
"hom": null,
"ns": null,
"vrt": null,
"main_data": "ƒ = 0.0000343",
"original_variant": "11-117222647-GA-G"
}
],
"saphetor_known_pathogenicity": [
{
"version": "05-May-2024",
"items": [
{
"annotations": {
"NCBI ClinVar2": [
{
"functions": [
"NMD",
"coding"
],
"coding_impact": "frameshift",
"acmg_confirmed": true,
"acmg_class": "Benign",
"acmg_reannotated": "Benign",
"source": "NCBI ClinVar2",
"codon": 116,
"gene_symbol": "CEP164",
"hgvs": "K116Rfs*22",
"transcript": "NM_014956.5",
"submission_count": 3,
"review_stars": 2,
"accession_count": 2,
"publication_count": 0,
"clinical_significance": [
"benign"
],
"disease_name": [
"Nephronophthisis 15",
"None Provided",
"Not Provided"
]
}
]
}
}
]
}
],
"acmg_annotation": {
"version_name": "11.15.0",
"gene_symbol": "CEP164",
"transcript": "NM_014956.5",
"transcript_reason": "MANE select",
"coding_impact": "frameshift",
"verdict": {
"ACMG_rules": {
"benign_score": 12,
"benign_subscore": "Benign",
"clinical_score": 1.2389999999999999,
"pathogenic_score": 1,
"pathogenic_subscore": "Uncertain Significance",
"total_score": -11,
"verdict": "Benign"
},
"classifications": [
"BA1",
"BP6_Strong",
"PVS1_Supporting"
]
},
"classifications": [
{
"name": "BA1",
"met_criteria": true,
"user_explain": [
"GnomAD exomes allele frequency = 0.0639 is greater than 0.05 threshold, good gnomAD exomes coverage = 54.3."
]
},
{
"name": "BP6",
"met_criteria": true,
"user_explain": [
"Combined evidence strength is Strong (score = 4).",
"Strong: ClinVar classifies this variant as Benign, 2 stars (reviewed Mar '23, 3 submissions of which 2 are from high confidence submitters)."
],
"strength": "Strong"
},
{
"name": "PVS1",
"met_criteria": true,
"user_explain": [
"Reduced strength as variant has BA1 frequency. null variant (frame-shift) in gene CEP164, predicted to cause NMD. Loss-of-function is a known mechanism of disease (gene has 76 reported pathogenic LOF variants). The exon affects 2 functional domains: UniProt protein CE164_HUMAN region of interest 'Disordered' and UniProt protein CE164_HUMAN region of interest 'Interaction with ATRIP'. The exon contains 8 pathogenic variants. The truncated region contains 69 pathogenic variants."
],
"strength": "Supporting"
}
],
"gene_id": 4000,
"sample_findings": {
"phenotypes": "No matching phenotype found for gene CEP164 which is associated with Ciliopathies, Ciliopathy, Ciliopathy Genes Associated With Cystic Kidney Disease, Genetic Retinal Degeneration Conditions and 7 more, according to CGD, ClinGen Disease Validity, GenCC, Mondo, PanelApp and gene2phenotype.",
"mode_of_inheritance": "AR, based on gene information from CGD, ClinGen Disease Validity, GenCC, Mondo, PanelApp and gene2phenotype."
}
},
"phylop100way": [
{
"version": "13-Apr-2021",
"conservation_score": [
"5.763",
"2.286",
"0.918",
"4.849",
"6.917",
"3.684",
"6.943",
"8.715",
"1.062",
"5.822",
"8.715"
]
}
],
"maxentscan": null
}