Variant rs10972300 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007126.5(VCP):c.129+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,607,896 control chromosomes in the GnomAD database, including 36,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2760 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33607 hom. )

Consequence

VCP
NM_007126.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.326

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:

ENSG00000288699 (HGNC:):

ENSG00000288699 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 9-35068204-C-T is Benign according to our data. Variant chr9-35068204-C-T is described in ClinVar as [Benign]. Clinvar id is 260121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
VCP	NM_007126.5 link	c.129+47G>A	intron_variant	ENST00000358901.11	NP_009057.1
VCP	NM_001354927.2 link	c.-7+47G>A	intron_variant		NP_001341856.1
VCP	NM_001354928.2 link	c.-7+47G>A	intron_variant		NP_001341857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCP	ENST00000358901.11 link	c.129+47G>A		intron_variant		1	NM_007126.5	ENSP00000351777.6		P55072
ENSG00000288699	ENST00000681845.1 link	n.*227+47G>A		intron_variant				ENSP00000505452.1		A0A7P0T910

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27373

AN:

152014

Hom.:

2756

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.0785

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.185

AC:

46549

AN:

251214

Hom.:

4694

AF XY:

0.190

AC XY:

25824

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.163

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.0816

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.210

AC:

306066

AN:

1455764

Hom.:

33607

Cov.:

AF XY:

0.210

AC XY:

152479

AN XY:

724646

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.0645

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.180

AC:

27401

AN:

152132

Hom.:

2760

Cov.:

AF XY:

0.177

AC XY:

13175

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.0785

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.205

Hom.:

3441

Bravo

AF:

0.183

Asia WGS

AF:

0.148

AC:

518

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Frontotemporal dementia and/or amyotrophic lateral sclerosis 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Charcot-Marie-Tooth disease type 2Y

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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