rs17886199
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_024006.6(VKORC1):c.283+186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 152,186 control chromosomes in the GnomAD database, including 48 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 0.013 ( 48 hom., cov: 31)
Consequence
VKORC1
NM_024006.6 intron
NM_024006.6 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.155
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1947/152186) while in subpopulation AFR AF= 0.0447 (1854/41516). AF 95% confidence interval is 0.043. There are 48 homozygotes in gnomad4. There are 894 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 48 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VKORC1 | NM_024006.6 | c.283+186T>C | intron_variant | ENST00000394975.3 | |||
VKORC1 | NM_001311311.2 | c.283+186T>C | intron_variant | ||||
VKORC1 | NM_206824.3 | c.173+1431T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VKORC1 | ENST00000394975.3 | c.283+186T>C | intron_variant | 1 | NM_024006.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0128 AC: 1942AN: 152068Hom.: 48 Cov.: 31
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.0128 AC: 1947AN: 152186Hom.: 48 Cov.: 31 AF XY: 0.0120 AC XY: 894AN XY: 74420
GnomAD4 genome
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894
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74420
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at