rs17882023

Positions:

• chr16-31092015-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024006.6(VKORC1):​c.284-673A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 151,654 control chromosomes in the GnomAD database, including 746 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.079 (746 hom., cov: 31)
• Consequence: VKORC1 NM_024006.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707

Genes affected

VKORC1 (HGNC:23663): (vitamin K epoxide reductase complex subunit 1) This gene encodes the catalytic subunit of the vitamin K epoxide reductase complex, which is responsible for the reduction of inactive vitamin K 2,3-epoxide to active vitamin K in the endoplasmic reticulum membrane. Vitamin K is a required co-factor for carboxylation of glutamic acid residues by vitamin K-dependent gamma-carboxylase in blood-clotting enzymes. Allelic variation in this gene is associated with vitamin k-dependent clotting factors combined deficiency of 2, and increased resistance or sensitivity to warfarin, an inhibitor of vitamin K epoxide reductase. Pseudogenes of this gene are located on chromosomes 1 and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

ENSG00000255439 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VKORC1	NM_024006.6	c.284-673A>G		intron_variant		ENST00000394975.3	NP_076869.1
VKORC1	NM_001311311.2	c.368-673A>G		intron_variant			NP_001298240.1
VKORC1	NM_206824.3	c.174-673A>G		intron_variant			NP_996560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VKORC1	ENST00000394975.3	c.284-673A>G		intron_variant		1	NM_024006.6	ENSP00000378426.2
ENSG00000255439	ENST00000529564.1	c.283+1297A>G		intron_variant		4		ENSP00000431371.1

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11917 AN: 151540 Hom.: 742 Cov.: 31

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0503

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0949

Gnomad OTH AF: 0.0792

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0786 AC: 11927 AN: 151654 Hom.: 746 Cov.: 31 AF XY: 0.0819 AC XY: 6069 AN XY: 74090

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0503

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0678

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.0779

Alfa AF: 0.0976 Hom.: 120

Bravo AF: 0.0768

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17882023; hg19: chr16-31103336;