VCV000226016.8 - ClinVar

NM_024006.6(VKORC1):c.*134G>A

Germline

Top reviewed classifications are shown here.

Submission summary:

2 submissions

2 submitters

2 conditions

Reviewed by expert panel

Drug response

Mar 2021 by PharmGKB

for warfarin response - Dosage

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_024006.6(VKORC1):c.*134G>A

Variation ID: 226016 Accession: VCV000226016.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16p11.2 16: 31091000 (GRCh38) [ NCBI UCSC ] 16: 31102321 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	May 22, 2016	Dec 12, 2021	Mar 24, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_024006.6:c.*134G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NM_001311311.2:c.*134G>A		3 prime UTR
NM_206824.3:c.*237G>A		3 prime UTR
NC_000016.10:g.31091000C>T
NC_000016.9:g.31102321C>T
NG_011564.1:g.8956G>A
LRG_582:g.8956G>A
LRG_582t1:c.*134G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000016.10:31090999:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.41973 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.39468

The Genome Aggregation Database (gnomAD) 0.39850

1000 Genomes Project 0.41973

1000 Genomes Project 30x 0.42661

Links

PharmGKB Clinical Annotation: 1445585748 PharmGKB Clinical Annotation: 655384733 ClinGen: CA10576177 dbSNP: rs7294 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
VKORC1		-	-	GRCh38 GRCh37	50	71

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
warfarin response - Dosage	drug response (1)	reviewed by expert panel	Mar 24, 2021	RCV000211278.11
Vitamin K-dependent clotting factors, combined deficiency of, type 2	Benign (1)	criteria provided, single submitter	Jan 12, 2018	RCV000295118.13

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
drug response (Mar 24, 2021)	reviewed by expert panel (Pharmacogenomics knowledge for personalized medicine) Method: curation	warfarin response - Dosage Affected status: yes Allele origin: germline	PharmGKB Accession: SCV000268386.4 First in ClinVar: May 22, 2016 Last updated: Dec 12, 2021	Publications: PubMed (19) PubMed: 15358623‚ 15883587‚ 16270629‚ 16611750‚ 16676068‚ 17049586‚ 18466099‚ 20128861‚ 20653676‚ 21127708‚ 21326313‚ 21635147‚ 22349464‚ 23208322‚ 23990957‚ 24019055‚ 25084205‚ 25126975‚ 25594941 Other databases https://www.pharmgkb.org/variant… https://www.pharmgkb.org/variant/PA166154977 https://www.pharmgkb.org/clinica… https://www.pharmgkb.org/clinicalAnnotation/655384733 Comment: PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing … (more) PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing guidance in an annotated clinical guideline or FDA drug label. Level 1B clinical annotations must be supported by at least two independent publications. (less)
Benign (Jan 12, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Vitamin K-dependent clotting factors, combined deficiency of, type 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000396617.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)

Comment:

PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing guidance in an annotated clinical guideline or FDA drug label. Level 1B clinical annotations must be supported by at least two independent publications.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Warfarin dosage response related pharmacogenetics in Chinese population.	Li S	PloS one	2015	PMID: 25594941
A pharmacogenetics-based warfarin maintenance dosing algorithm from Northern Chinese patients.	Chen J	PloS one	2014	PMID: 25126975
Methodological issues in the development of a pharmacogenomic algorithm for warfarin dosing: comparison of two regression approaches.	Pavani A	Pharmacogenomics	2014	PMID: 25084205
Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on warfarin maintenance dose and explicating a new pharmacogenetic algorithm in South Indian population.	Krishna Kumar D	European journal of clinical pharmacology	2014	PMID: 24019055
Warfarin anticoagulant therapy: a Southern Italy pharmacogenetics-based dosing model.	Mazzaccara C	PloS one	2013	PMID: 23990957
Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage.	Wang LS	European journal of clinical pharmacology	2013	PMID: 23208322
A new warfarin dosing algorithm including VKORC1 3730 G > A polymorphism: comparison with results obtained by other published algorithms.	Cini M	European journal of clinical pharmacology	2012	PMID: 22349464
Novel CYP2C9 and VKORC1 gene variants associated with warfarin dosage variability in the South African black population.	Mitchell C	Pharmacogenomics	2011	PMID: 21635147
Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients.	Choi JR	Journal of human genetics	2011	PMID: 21326313
Genetic variation of VKORC1 and CYP4F2 genes related to warfarin maintenance dose in patients with myocardial infarction.	Kringen MK	Journal of biomedicine & biotechnology	2011	PMID: 21127708
CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement.	Cen HJ	British journal of clinical pharmacology	2010	PMID: 20653676
Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population.	Lubitz SA	Journal of thrombosis and haemostasis : JTH	2010	PMID: 20128861
Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans.	Limdi NA	Pharmacogenomics	2008	PMID: 18466099
Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients.	Kimura R	Thrombosis research	2007	PMID: 17049586
The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement.	Herman D	Thrombosis and haemostasis	2006	PMID: 16676068
Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation.	Li T	Journal of medical genetics	2006	PMID: 16611750
VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation.	Geisen C	Thrombosis and haemostasis	2005	PMID: 16270629
Common VKORC1 and GGCX polymorphisms associated with warfarin dose.	Wadelius M	The pharmacogenomics journal	2005	PMID: 15883587
A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin.	D'Andrea G	Blood	2005	PMID: 15358623
https://www.pharmgkb.org/clinicalAnnotation/655384733	-	-	-	-
https://www.pharmgkb.org/variant/PA166154977	-	-	-	-
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Text-mined citations for rs7294 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_024006.6(VKORC1):c.*134G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs7294 ...