rs10972300
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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
NM_007126.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.326
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]
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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 | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCP | NM_007126.5 | c.129+47G>A | intron_variant | ENST00000358901.11 | |||
VCP | NM_001354927.2 | c.-7+47G>A | intron_variant | ||||
VCP | NM_001354928.2 | c.-7+47G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCP | ENST00000358901.11 | c.129+47G>A | intron_variant | 1 | NM_007126.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.180 AC: 27373AN: 152014Hom.: 2756 Cov.: 32
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GnomAD3 exomes AF: 0.185 AC: 46549AN: 251214Hom.: 4694 AF XY: 0.190 AC XY: 25824AN XY: 135808
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GnomAD4 exome AF: 0.210 AC: 306066AN: 1455764Hom.: 33607 Cov.: 30 AF XY: 0.210 AC XY: 152479AN XY: 724646
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GnomAD4 genome ? AF: 0.180 AC: 27401AN: 152132Hom.: 2760 Cov.: 32 AF XY: 0.177 AC XY: 13175AN XY: 74368
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
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 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2018 | - - |
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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at