9-35068643-A-T

Variant names:

• chr9-35068643-A-T
• rs2073575
• NM_007126.5:c.18-281T>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007126.5(VCP):​c.18-281T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 152,248 control chromosomes in the GnomAD database, including 578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.067 (578 hom., cov: 32)
• Consequence: VCP NM_007126.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.465

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]

ENSG00000288699 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-35068643-A-T is Benign according to our data. Variant chr9-35068643-A-T is described in ClinVar as [Benign]. Clinvar id is 1228992.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCP	NM_007126.5	c.18-281T>A		intron_variant	Intron 1 of 16	ENST00000358901.11	NP_009057.1
VCP	NM_001354927.2	c.-118-281T>A		intron_variant	Intron 1 of 16		NP_001341856.1
VCP	NM_001354928.2	c.-118-281T>A		intron_variant	Intron 1 of 16		NP_001341857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCP	ENST00000358901.11	c.18-281T>A		intron_variant	Intron 1 of 16	1	NM_007126.5	ENSP00000351777.6
ENSG00000288699	ENST00000681845.1	n.*116-281T>A		intron_variant	Intron 1 of 4			ENSP00000505452.1

Frequencies

GnomAD3 genomes AF: 0.0674 AC: 10260 AN: 152130 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.0402

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0674 AC: 10262 AN: 152248 Hom.: 578 Cov.: 32 AF XY: 0.0719 AC XY: 5350 AN XY: 74456

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.0780

Gnomad4 ASJ AF: 0.0897

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0938

Gnomad4 NFE AF: 0.0531

Gnomad4 OTH AF: 0.0706

Alfa AF: 0.0275 Hom.: 21

Bravo AF: 0.0687

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.84

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

Other links and lift over

dbSNP: rs2073575; hg19: chr9-35068640;