chr8-99507809-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_017890.5(VPS13B):āc.4197T>Cā(p.Gly1399=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0025 in 1,613,908 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0053 ( 14 hom., cov: 33)
Exomes š: 0.0022 ( 133 hom. )
Consequence
VPS13B
NM_017890.5 synonymous
NM_017890.5 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 4.71
Genes affected
VPS13B (HGNC:2183): (vacuolar protein sorting 13 homolog B) This gene encodes a potential transmembrane protein that may function in vesicle-mediated transport and sorting of proteins within the cell. This protein may play a role in the development and the function of the eye, hematological system, and central nervous system. Mutations in this gene have been associated with Cohen syndrome. Multiple splice variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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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=-0.47).
BP6
Variant 8-99507809-T-C is Benign according to our data. Variant chr8-99507809-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 95852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.4197T>C | p.Gly1399= | synonymous_variant | 28/62 | ENST00000358544.7 | |
VPS13B | NM_152564.5 | c.4224+606T>C | intron_variant | ENST00000357162.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000358544.7 | c.4197T>C | p.Gly1399= | synonymous_variant | 28/62 | 1 | NM_017890.5 | ||
VPS13B | ENST00000357162.7 | c.4224+606T>C | intron_variant | 1 | NM_152564.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00532 AC: 808AN: 152012Hom.: 14 Cov.: 33
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GnomAD3 exomes AF: 0.0104 AC: 2624AN: 251348Hom.: 121 AF XY: 0.00788 AC XY: 1070AN XY: 135840
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GnomAD4 exome AF: 0.00220 AC: 3223AN: 1461778Hom.: 133 Cov.: 31 AF XY: 0.00181 AC XY: 1315AN XY: 727198
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GnomAD4 genome AF: 0.00530 AC: 806AN: 152130Hom.: 14 Cov.: 33 AF XY: 0.00629 AC XY: 468AN XY: 74396
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cohen syndrome Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 09, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 27, 2013 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 14, 2016 | This alteration is classified as 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
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