rs17883590

Variant names:

• chr16-31095206-C-T
• rs17883590
• XM_047435012.1:c.173G>A
• LOC124903680 p.Gly58Asp

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000420057.2(VKORC1):​c.243+183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,210,968 control chromosomes in the GnomAD database, including 6 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 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (3 hom.)
• Consequence: VKORC1 ENST00000420057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529
• Publications: 2 publications found

Genes affected

LOC124903680 (HGNC:):

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]

VKORC1 Gene-Disease associations (from GenCC):

• vitamin K-dependent clotting factors, combined deficiency of, type 2

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• vitamin K-dependent clotting factors, combined deficiency of, type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Homozygotes in GnomAd4 at 3 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000420057.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VKORC1	ENST00000498155.1	TSL:5	c.270+183G>A		intron	N/A	ENSP00000417662.1	F2Z3Q2
	VKORC1	ENST00000420057.2	TSL:2	c.243+183G>A		intron	N/A	ENSP00000437064.1	H0YF24
	ENSG00000280160	ENST00000624508.1	TSL:6	n.1480C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00396 AC: 602 AN: 152072 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000342 AC: 362 AN: 1058778 Hom.: 3 Cov.: 14 AF XY: 0.000291 AC XY: 151 AN XY: 519100

African (AFR) AF: 0.0120 AC: 284 AN: 23640

American (AMR) AF: 0.00103 AC: 18 AN: 17554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16424

East Asian (EAS) AF: 0.00 AC: 0 AN: 30098

South Asian (SAS) AF: 0.0000887 AC: 5 AN: 56388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26610

Middle Eastern (MID) AF: 0.000651 AC: 2 AN: 3070

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 840576

Other (OTH) AF: 0.00113 AC: 50 AN: 44418

GnomAD4 genome AF: 0.00394 AC: 600 AN: 152190 Hom.: 3 Cov.: 32 AF XY: 0.00382 AC XY: 284 AN XY: 74404

African (AFR) AF: 0.0135 AC: 562 AN: 41516

American (AMR) AF: 0.00196 AC: 30 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00284 Hom.: 1

Bravo AF: 0.00476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.67
PhyloP100		0.53
PromoterAI		-0.038	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17883590;

hg19: chr16-31106527;