Variant 9-35056964-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_007126.5(VCP):c.*153G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 761,896 control chromosomes in the GnomAD database, including 16,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3031 hom., cov: 33)

Exomes 𝑓: 0.20 ( 13052 hom. )

Consequence

VCP
NM_007126.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.395

Variant links:

Genes affected

VCP (HGNC:12666): (valosin containing protein) This gene encodes a member of the AAA ATPase family of proteins. The encoded protein plays a role in protein degradation, intracellular membrane fusion, DNA repair and replication, regulation of the cell cycle, and activation of the NF-kappa B pathway. This protein forms a homohexameric complex that interacts with a variety of cofactors and extracts ubiquitinated proteins from lipid membranes or protein complexes. Mutations in this gene cause IBMPFD (inclusion body myopathy with paget disease of bone and frontotemporal dementia), ALS (amyotrophic lateral sclerosis) and Charcot-Marie-Tooth disease in human patients. [provided by RefSeq, Aug 2017]

VCP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 9-35056964-C-A is Benign according to our data. Variant chr9-35056964-C-A is described in ClinVar as [Benign]. Clinvar id is 366714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
VCP	NM_007126.5 linkuse as main transcript	c.*153G>T	3_prime_UTR_variant	17/17	ENST00000358901.11
VCP	NM_001354927.2 linkuse as main transcript	c.*153G>T	3_prime_UTR_variant	17/17
VCP	NM_001354928.2 linkuse as main transcript	c.*153G>T	3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCP	ENST00000358901.11 linkuse as main transcript	c.*153G>T		3_prime_UTR_variant	17/17	1	NM_007126.5	P3

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29167

AN:

152102

Hom.:

3028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.0778

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.195

GnomAD4 exome

AF:

0.201

AC:

122490

AN:

609676

Hom.:

13052

Cov.:

AF XY:

0.203

AC XY:

66166

AN XY:

325748

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.281

Gnomad4 EAS exome

AF:

0.0617

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.206

GnomAD4 genome

AF:

0.192

AC:

29187

AN:

152220

Hom.:

3031

Cov.:

AF XY:

0.188

AC XY:

13995

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.0778

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.206

Hom.:

4045

Bravo

AF:

0.196

Asia WGS

AF:

0.147

AC:

513

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Frontotemporal dementia and/or amyotrophic lateral sclerosis 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over