VCV000284302.24 - ClinVar

NM_007126.5(VCP):c.79A>G (p.Ile27Val)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(9)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007126.5(VCP):c.79A>G (p.Ile27Val)

Variation ID: 284302 Accession: VCV000284302.24

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9p13.3 9: 35068301 (GRCh38) [ NCBI UCSC ] 9: 35068298 (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	Dec 6, 2016	Oct 8, 2024	Jan 28, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_007126.5:c.79A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_009057.1:p.Ile27Val	missense
NM_001354927.2:c.-57A>G		5 prime UTR
NM_001354928.2:c.-57A>G		5 prime UTR
NC_000009.12:g.35068301T>C
NC_000009.11:g.35068298T>C
NG_007887.1:g.9442A>G
LRG_657:g.9442A>G
LRG_657t1:c.79A>G

... more HGVS ... less HGVS

Protein change

I27V

Other names

Canonical SPDI

NC_000009.12:35068300:T:C

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.

0.00100 (C)

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

Exome Aggregation Consortium (ExAC) 0.00054

The Genome Aggregation Database (gnomAD), exomes 0.00055

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00092

1000 Genomes Project 30x 0.00094

1000 Genomes Project 0.00100

The Genome Aggregation Database (gnomAD) 0.00151

Trans-Omics for Precision Medicine (TOPMed) 0.00158

Links

ClinGen: CA5039558 dbSNP: rs140913250 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.
VCP		-	-	GRCh38 GRCh37	614	700

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.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 Inclusion body myopathy with Paget disease of bone and frontotemporal dementia	Benign (1)	criteria provided, single submitter	Jan 28, 2024	RCV000639655.11
not specified	Benign (1)	criteria provided, single submitter	Apr 19, 2017	RCV000390549.5
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1	Benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV001168987.5
Intellectual disability	Uncertain significance (1)	no assertion criteria provided	Jan 1, 2019	RCV001252623.3
Frontotemporal dementia and/or amyotrophic lateral sclerosis 6	Benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV001168490.5
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Jan 18, 2021	RCV001642885.4
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	May 20, 2020	RCV002418113.3
VCP-related disorder	Likely benign (1)	no assertion criteria provided	Nov 12, 2021	RCV004543043.2

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.
Benign (Apr 19, 2017)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000336872.4 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016	Publications: PubMed (1) PubMed: 25617006 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=VCP http://gnomad.broadinstitute.org… http://gnomad.broadinstitute.org/region/9-35068198-35068398 Number of individuals with the variant: 2 Sex: mixed
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001331084.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: 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, … (more) 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001331632.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Publications: PubMed (3) PubMed: 21920633‚ 25617006‚ 21387114 Comment: 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, … (more) 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
Benign (Jan 18, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001860065.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Comment: This variant is associated with the following publications: (PMID: 30279455, 28430856, 21387114, 21920633, 25617006, 28542158, 31996268)
Benign (Jan 28, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000761235.7 First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024
Likely benign (May 20, 2020)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002678644.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005272588.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Uncertain significance (Jan 01, 2019)	no assertion criteria provided Method: clinical testing	Intellectual disability Affected status: yes Allele origin: unknown	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille Accession: SCV001428384.1 First in ClinVar: Aug 15, 2020 Last updated: Aug 15, 2020	Publications: PubMed (1) PubMed: 25741868
Likely benign (Nov 12, 2021)	no assertion criteria provided Method: clinical testing	VCP-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004777136.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: 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).

Comment:

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

Comment:

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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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:

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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.	Richards S	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25741868
Targeted sequencing and identification of genetic variants in sporadic inclusion body myositis.	Weihl CC	Neuromuscular disorders : NMD	2015	PMID: 25617006
Mutational analysis of the VCP gene in Parkinson's disease.	Majounie E	Neurobiology of aging	2012	PMID: 21920633
A novel exon 2 I27V VCP variant is associated with dissimilar clinical syndromes.	Rohrer JD	Journal of neurology	2011	PMID: 21387114
http://gnomad.broadinstitute.org/region/9-35068198-35068398	-	-	-	-
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=VCP	-	-	-	-

Text-mined citations for rs140913250 ...

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_007126.5(VCP):c.79A>G (p.Ile27Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs140913250 ...