rs7294

chr16-31091000-C-T

• Frequency: Genomes: 𝑓 0.40 (12858 hom., cov: 31)
• Consequence: VKORC1 NM_024006 3_prime_UTR
• Clinical Significance: drug response reviewed by expert panel B:1 O:1
• Conservation: PhyloP100: 0.00200

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16:31091000-C>T is Benign according to our data. Variant chr16-31091000-C-T is described in ClinVar as [drug_response]. Clinvar id is 226016. Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Benign=1, drug_response=1}.
• BA1: GnomAd highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VKORC1	NM_024006.6	c.*134G>A		3_prime_UTR_variant	3/3	ENST00000394975.3
VKORC1	NM_001311311.2	c.*134G>A		3_prime_UTR_variant	4/4
VKORC1	NM_206824.3	c.*237G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VKORC1	ENST00000394975.3	c.*134G>A		3_prime_UTR_variant	3/3	1	NM_024006.6	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61172 AN: 151832 Hom.: 12858 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.390 AC: 496903 AN: 1274084 Hom.: 102978 AF XY: 0.397 AC XY: 250851 AN XY: 631166

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.0949

Gnomad4 SAS exome AF: 0.686

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.380

Alfa AF: 0.379 Hom.: 19249

Bravo AF: 0.395

Asia WGS AF: 0.458 AC: 1591 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Benign:1Other:1

Revision: reviewed by expert panel

LINK:

Submissions by phenotype

Vitamin K-dependent clotting factors, combined deficiency of, type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

warfarin response - Dosage 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: Dosage

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

Cadd

Benign

1.5

Dann

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7294; hg19: chr16-31102321;