16-31096368-C-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_StrongBA1
The variant allele was found at a frequency of 0.319 in 152,092 control chromosomes in the GnomAD database, including 10,015 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).
Frequency
Genomes: 𝑓 0.32 ( 10015 hom., cov: 32)
Consequence
Unknown
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.417
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 16-31096368-C-T is Benign according to our data. Variant chr16-31096368-C-T is described in ClinVar as [drug_response]. Clinvar id is 2211.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {other=1, drug_response=6, Likely_benign=2}.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.
Transcripts
RefSeq
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Ensembl
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Frequencies
GnomAD3 genomes ? AF: 0.319 AC: 48521AN: 151974Hom.: 10014 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.319 AC: 48520AN: 152092Hom.: 10015 Cov.: 32 AF XY: 0.322 AC XY: 23921AN XY: 74344
GnomAD4 genome
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48520
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32
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23921
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74344
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1603
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3478
ClinVar
Significance: drug response
Submissions summary: Pathogenic:1Uncertain:2Benign:3Other:8
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Warfarin response Pathogenic:1Other:1
drug response, no assertion criteria provided | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 16, 2006 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2010 | - - |
Thrombus Uncertain:1
Uncertain significance, no assertion criteria provided | case-control;research | Department of Pharmacology - Sarajevo Medical School, University Sarajevo School of Science and Technology | - | - - |
See cases Uncertain:1
Uncertain significance, no assertion criteria provided | case-control | Department of Pharmacology - Sarajevo Medical School, University Sarajevo School of Science and Technology | - | It is uncertain if there exists an association between the presence of the variant or A allele, at the VKORC1 -1639G>A locus, and survival from thromboembolism in COVID-19 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 09, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
VKORC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 20, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Venous thromboembolism Benign:1
protective, no assertion criteria provided | research | Faculty of Pharmacy, Damascus University | - | Some studies observed an association between VKORC1 -1639G>A (rs9923231) with thromboembolism (Dubovyk 2016, Kumari 2019). Our study suggests a possible protective effect for the -1639A allele against venous thromboembolism. References Dubovyk YI, Harbuzova VY, Ataman A V. G-1639A but Not C1173T VKORC1 Gene Polymorphism is Related to Ischemic Stroke and Its Various Risk Factors in Ukrainian Population. Biomed Res Int. 2016 Sep 15;2016. Kumari B, Garg I, Rai C, Panjawani U, Bhuvnesh K, Srivastava S. Positive Association of Mutations in VKORC1 and CYP2C9 Genes with Venous Thrombo-Embolism (VTE) in Indian Population: A Case Control Study. J Genet Eng Biotechnol Res. 2019;1(2). - |
phenprocoumon response - Toxicity Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Toxicity |
warfarin response - Dosage Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Nov 19, 2021 | PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Dosage |
phenprocoumon response - Dosage Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Dosage |
acenocoumarol response - Dosage Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Dosage |
not provided Other:1
other, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 08, 2018 | - Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles). |
warfarin response - Toxicity Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing guidance in an annotated clinical guideline or FDA drug label. Level 1B clinical annotations must be supported by at least two independent publications. Drug-variant association: Toxicity |
warfarin response - Efficacy Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at