rs565070

Positions:

• chr9-35054589-G-A
• chr9-35054589-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000679902.1(VCP):​c.*2783C>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 0.484 in 152,034 control chromosomes in the GnomAD database, including 18,543 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18543 hom., cov: 32)
• Consequence: VCP ENST00000679902.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCP	ENST00000679902.1	c.*2783C>T		3_prime_UTR_variant	16/16			ENSP00000506338

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73551 AN: 151916 Hom.: 18533 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.484 AC: 73582 AN: 152034 Hom.: 18543 Cov.: 32 AF XY: 0.485 AC XY: 36062 AN XY: 74292

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.497

Alfa AF: 0.544 Hom.: 22118

Bravo AF: 0.479

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs565070; hg19: chr9-35054586; COSMIC: COSV62719980;