rs114818249
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_017890.5(VPS13B):c.10899C>T(p.His3633=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000281 in 1,614,050 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 1 hom. )
Consequence
VPS13B
NM_017890.5 synonymous
NM_017890.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.64
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 -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 8-99854213-C-T is Benign according to our data. Variant chr8-99854213-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-99854213-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.64 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.10899C>T | p.His3633= | synonymous_variant | 56/62 | ENST00000358544.7 | NP_060360.3 | |
VPS13B | NM_152564.5 | c.10824C>T | p.His3608= | synonymous_variant | 56/62 | ENST00000357162.7 | NP_689777.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000358544.7 | c.10899C>T | p.His3633= | synonymous_variant | 56/62 | 1 | NM_017890.5 | ENSP00000351346 | ||
VPS13B | ENST00000357162.7 | c.10824C>T | p.His3608= | synonymous_variant | 56/62 | 1 | NM_152564.5 | ENSP00000349685 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00116 AC: 176AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000323 AC: 81AN: 250982Hom.: 1 AF XY: 0.000199 AC XY: 27AN XY: 135664
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GnomAD4 exome AF: 0.000188 AC: 275AN: 1461802Hom.: 1 Cov.: 32 AF XY: 0.000157 AC XY: 114AN XY: 727190
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GnomAD4 genome AF: 0.00117 AC: 178AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.00110 AC XY: 82AN XY: 74436
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | VPS13B: BP4, BP7 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 17, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Cohen syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2017 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at