chr16-31093850-G-A

Position:

• chr16-31093850-G-A

Variant summary

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

The NM_024006.6(VKORC1):​c.174-429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00993 in 285,144 control chromosomes in the GnomAD database, including 91 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 0.017 (85 hom., cov: 29)
  • Exomes 𝑓: 0.0023 (6 hom.)
• Consequence: VKORC1 NM_024006.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VKORC1	NM_024006.6	c.174-429C>T		intron_variant		ENST00000394975.3
VKORC1	NM_001311311.2	c.174-429C>T		intron_variant
VKORC1	NM_206824.3	c.173+707C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VKORC1	ENST00000394975.3	c.174-429C>T		intron_variant		1	NM_024006.6	P1
	ENST00000624508.1	n.124G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2522 AN: 150276 Hom.: 85 Cov.: 29

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00604

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000253

Gnomad OTH AF: 0.00977

GnomAD4 exome AF: 0.00226 AC: 305 AN: 134770 Hom.: 6 Cov.: 4 AF XY: 0.00170 AC XY: 121 AN XY: 71338

Gnomad4 AFR exome AF: 0.0565

Gnomad4 AMR exome AF: 0.00361

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000156

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000856

Gnomad4 OTH exome AF: 0.00393

GnomAD4 genome AF: 0.0168 AC: 2527 AN: 150374 Hom.: 85 Cov.: 29 AF XY: 0.0166 AC XY: 1219 AN XY: 73320

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.00604

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000253

Gnomad4 OTH AF: 0.00967

Alfa AF: 0.00367 Hom.: 12

Bravo AF: 0.0190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.61

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: rs13336384; hg19: chr16-31105171;