NM_007126.5:c.1360-35A>G

Variant names:

Variant summary

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

The NM_007126.5(VCP):c.1360-35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,613,946 control chromosomes in the GnomAD database, including 475,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43403 hom., cov: 32)

Exomes 𝑓: 0.77 ( 432270 hom. )

Consequence

VCP
NM_007126.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.536

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 9-35060958-T-C is Benign according to our data. Variant chr9-35060958-T-C is described in ClinVar as [Benign]. Clinvar id is 260123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
VCP	NM_007126.5 link	c.1360-35A>G	intron_variant	Intron 11 of 16	ENST00000358901.11	NP_009057.1
VCP	NM_001354927.2 link	c.1225-35A>G	intron_variant	Intron 11 of 16		NP_001341856.1
VCP	NM_001354928.2 link	c.1225-35A>G	intron_variant	Intron 11 of 16		NP_001341857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCP	ENST00000358901.11 link	c.1360-35A>G		intron_variant	Intron 11 of 16	1	NM_007126.5	ENSP00000351777.6		P55072

Frequencies

GnomAD3 genomes

AF:

0.753

AC:

114391

AN:

151982

Hom.:

43374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.705

Gnomad AMR

AF:

0.795

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.780

Gnomad OTH

AF:

0.752

GnomAD3 exomes

AF:

0.748

AC:

188166

AN:

251462

Hom.:

71612

AF XY:

0.746

AC XY:

101417

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.742

Gnomad AMR exome

AF:

0.844

Gnomad ASJ exome

AF:

0.791

Gnomad EAS exome

AF:

0.455

Gnomad SAS exome

AF:

0.709

Gnomad FIN exome

AF:

0.721

Gnomad NFE exome

AF:

0.778

Gnomad OTH exome

AF:

0.765

GnomAD4 exome

AF:

0.767

AC:

1120704

AN:

1461846

Hom.:

432270

Cov.:

AF XY:

0.766

AC XY:

556761

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.748

Gnomad4 AMR exome

AF:

0.841

Gnomad4 ASJ exome

AF:

0.791

Gnomad4 EAS exome

AF:

0.492

Gnomad4 SAS exome

AF:

0.713

Gnomad4 FIN exome

AF:

0.719

Gnomad4 NFE exome

AF:

0.781

Gnomad4 OTH exome

AF:

0.752

GnomAD4 genome

AF:

0.753

AC:

114472

AN:

152100

Hom.:

43403

Cov.:

AF XY:

0.748

AC XY:

55622

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.740

Gnomad4 AMR

AF:

0.795

Gnomad4 ASJ

AF:

0.796

Gnomad4 EAS

AF:

0.462

Gnomad4 SAS

AF:

0.708

Gnomad4 FIN

AF:

0.719

Gnomad4 NFE

AF:

0.780

Gnomad4 OTH

AF:

0.747

Alfa

AF:

0.777

Hom.:

9666

Bravo

AF:

0.759

Asia WGS

AF:

0.584

AC:

2031

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Frontotemporal dementia and/or amyotrophic lateral sclerosis 6

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease type 2Y

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.93

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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