16-31093188-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_024006.6(VKORC1):c.283+124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000392 in 1,026,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00040 (0 hom.)
• Consequence: VKORC1 NM_024006.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.576

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-31093188-C-T is Benign according to our data. Variant chr16-31093188-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316884.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VKORC1	NM_024006.6	c.283+124G>A		intron_variant		ENST00000394975.3
VKORC1	NM_001311311.2	c.283+124G>A		intron_variant
VKORC1	NM_206824.3	c.173+1369G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VKORC1	ENST00000394975.3	c.283+124G>A		intron_variant		1	NM_024006.6	P1

Frequencies

GnomAD3 genomes AF: 0.000331 AC: 49 AN: 148206 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00493

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000403 AC: 354 AN: 878652 Hom.: 0 AF XY: 0.000420 AC XY: 188 AN XY: 447668

Gnomad4 AFR exome AF: 0.000220

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00523

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000617

Gnomad4 FIN exome AF: 0.000332

Gnomad4 NFE exome AF: 0.000308

Gnomad4 OTH exome AF: 0.000878

GnomAD4 genome AF: 0.000331 AC: 49 AN: 148206 Hom.: 0 Cov.: 28 AF XY: 0.000277 AC XY: 20 AN XY: 72084

Gnomad4 AFR AF: 0.000125

Gnomad4 AMR AF: 0.000137

Gnomad4 ASJ AF: 0.00493

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000102

Gnomad4 NFE AF: 0.000356

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000125 Hom.: 6711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.5
Dann	Benign	0.72

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: rs8050894; hg19: chr16-31104509;