rs545008110
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_017890.5(VPS13B):c.7322+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,826 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000030 ( 1 hom. )
Consequence
VPS13B
NM_017890.5 intron
NM_017890.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.883
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 Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 8-99766979-T-C is Benign according to our data. Variant chr8-99766979-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 437239.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.7322+9T>C | intron_variant | ENST00000358544.7 | |||
VPS13B | NM_152564.5 | c.7247+9T>C | intron_variant | ENST00000357162.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000357162.7 | c.7247+9T>C | intron_variant | 1 | NM_152564.5 | P1 | |||
VPS13B | ENST00000358544.7 | c.7322+9T>C | intron_variant | 1 | NM_017890.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152168Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000559 AC: 14AN: 250640Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135498
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1460540Hom.: 1 Cov.: 30 AF XY: 0.0000482 AC XY: 35AN XY: 726702
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152286Hom.: 0 Cov.: 31 AF XY: 0.0000806 AC XY: 6AN XY: 74442
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Cohen syndrome Benign:2
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 13, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 13, 2016 | - - |
Computational scores
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Name
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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