rs17708472
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_024006.6(VKORC1):c.173+525C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 961,844 control chromosomes in the GnomAD database, including 21,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.16 ( 2529 hom., cov: 30)
Exomes 𝑓: 0.20 ( 18737 hom. )
Consequence
VKORC1
NM_024006.6 intron
NM_024006.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.914
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 16-31094032-G-A is Benign according to our data. Variant chr16-31094032-G-A is described in ClinVar as [Benign]. Clinvar id is 225960.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VKORC1 | NM_024006.6 | c.173+525C>T | intron_variant | ENST00000394975.3 | |||
VKORC1 | NM_001311311.2 | c.173+525C>T | intron_variant | ||||
VKORC1 | NM_206824.3 | c.173+525C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VKORC1 | ENST00000394975.3 | c.173+525C>T | intron_variant | 1 | NM_024006.6 | P1 | |||
ENST00000624508.1 | n.306G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.164 AC: 24884AN: 151630Hom.: 2529 Cov.: 30
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GnomAD4 exome AF: 0.204 AC: 165028AN: 810098Hom.: 18737 Cov.: 11 AF XY: 0.202 AC XY: 82709AN XY: 408682
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GnomAD4 genome ? AF: 0.164 AC: 24885AN: 151746Hom.: 2529 Cov.: 30 AF XY: 0.162 AC XY: 12012AN XY: 74138
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 13, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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