rs61742245
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 4P and 12B. PM1PM5BP4_StrongBP6_StrongBS2
The NM_024006.6(VKORC1):c.106G>T(p.Asp36Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,606,390 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D36G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_024006.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VKORC1 | NM_024006.6 | c.106G>T | p.Asp36Tyr | missense_variant | 1/3 | ENST00000394975.3 | |
VKORC1 | NM_001311311.2 | c.106G>T | p.Asp36Tyr | missense_variant | 1/4 | ||
VKORC1 | NM_206824.3 | c.106G>T | p.Asp36Tyr | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VKORC1 | ENST00000394975.3 | c.106G>T | p.Asp36Tyr | missense_variant | 1/3 | 1 | NM_024006.6 | P1 | |
ENST00000624508.1 | n.898C>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.00148 AC: 226AN: 152260Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.00240 AC: 547AN: 227482Hom.: 4 AF XY: 0.00235 AC XY: 295AN XY: 125414
GnomAD4 exome AF: 0.00134 AC: 1947AN: 1454012Hom.: 23 Cov.: 32 AF XY: 0.00143 AC XY: 1032AN XY: 723218
GnomAD4 genome ? AF: 0.00148 AC: 226AN: 152378Hom.: 4 Cov.: 32 AF XY: 0.00166 AC XY: 124AN XY: 74516
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | VKORC1: PM5, PP3, BS2 - |
Warfarin response Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2008 | - - |
Thrombus Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Vitamin K-dependent clotting factors, combined deficiency of, type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
VKORC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 29, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
warfarin response - Dosage Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Nov 18, 2021 | PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Dosage |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at