rs769455914
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_007126.5(VCP):c.552C>T(p.Cys184=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000254 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
VCP
NM_007126.5 synonymous
NM_007126.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.76
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 -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 9-35065275-G-A is Benign according to our data. Variant chr9-35065275-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 532764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000226 (33/1461882) while in subpopulation AMR AF= 0.000201 (9/44724). AF 95% confidence interval is 0.000104. There are 0 homozygotes in gnomad4_exome. There are 16 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCP | NM_007126.5 | c.552C>T | p.Cys184= | synonymous_variant | 5/17 | ENST00000358901.11 | |
VCP | NM_001354927.2 | c.417C>T | p.Cys139= | synonymous_variant | 5/17 | ||
VCP | NM_001354928.2 | c.417C>T | p.Cys139= | synonymous_variant | 5/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCP | ENST00000358901.11 | c.552C>T | p.Cys184= | synonymous_variant | 5/17 | 1 | NM_007126.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152136Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251484Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135918
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727244
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74302
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia;C5436279:Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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