16-31096368-C-T

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

drug response reviewed by expert panel P:1U:2B:4O:8

Conservation

PhyloP100: -0.417
Variant links:

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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: {Benign=1, drug_response=6, Likely_benign=1, other=1}.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt

Frequencies

GnomAD3 genomes
AF:
0.319
AC:
48521
AN:
151974
Hom.:
10014
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.100
Gnomad AMI
AF:
0.442
Gnomad AMR
AF:
0.391
Gnomad ASJ
AF:
0.499
Gnomad EAS
AF:
0.891
Gnomad SAS
AF:
0.178
Gnomad FIN
AF:
0.391
Gnomad MID
AF:
0.519
Gnomad NFE
AF:
0.378
Gnomad OTH
AF:
0.391
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.319
AC:
48520
AN:
152092
Hom.:
10015
Cov.:
32
AF XY:
0.322
AC XY:
23921
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0998
Gnomad4 AMR
AF:
0.391
Gnomad4 ASJ
AF:
0.499
Gnomad4 EAS
AF:
0.892
Gnomad4 SAS
AF:
0.178
Gnomad4 FIN
AF:
0.391
Gnomad4 NFE
AF:
0.378
Gnomad4 OTH
AF:
0.389
Alfa
AF:
0.381
Hom.:
15716
Bravo
AF:
0.323
Asia WGS
AF:
0.460
AC:
1603
AN:
3478

ClinVar

Significance: drug response
Submissions summary: Pathogenic:1Uncertain:2Benign:4Other:8
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Warfarin response Pathogenic:1Other:1
drug response, no assertion criteria providedclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineDec 16, 2006- -
Pathogenic, no assertion criteria providedliterature onlyOMIMSep 01, 2010- -
not provided Benign:1Other:1
other, criteria provided, single submitterclinical testingEurofins 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).
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 25, 2024- -
Thrombus Uncertain:1
Uncertain significance, no assertion criteria providedcase-control;researchDepartment of Pharmacology - Sarajevo Medical School, University Sarajevo School of Science and Technology-- -
See cases Uncertain:1
Uncertain significance, no assertion criteria providedcase-controlDepartment 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 submitterclinical testingGeneDxMar 09, 2018This 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, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 20, 2021This 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 providedresearchFaculty 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 panelcurationPharmGKBMar 24, 2021PharmGKB 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 panelcurationPharmGKBNov 19, 2021PharmGKB 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 panelcurationPharmGKBMar 24, 2021PharmGKB 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 panelcurationPharmGKBMar 24, 2021PharmGKB 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
warfarin response - Toxicity Other:1
drug response, reviewed by expert panelcurationPharmGKBMar 24, 2021PharmGKB 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 panelcurationPharmGKBMar 24, 2021PharmGKB 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
5.5
DANN
Benign
0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9923231; hg19: chr16-31107689; API