rs145648860
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_017890.5(VPS13B):āc.1782T>Cā(p.Ile594=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,614,034 control chromosomes in the GnomAD database, including 13 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 0.0063 ( 8 hom., cov: 32)
Exomes š: 0.00058 ( 5 hom. )
Consequence
VPS13B
NM_017890.5 synonymous
NM_017890.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.23
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 8-99143104-T-C is Benign according to our data. Variant chr8-99143104-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 528869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.23 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00632 (963/152298) while in subpopulation AFR AF= 0.0217 (904/41566). AF 95% confidence interval is 0.0206. There are 8 homozygotes in gnomad4. There are 468 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.1782T>C | p.Ile594= | synonymous_variant | 13/62 | ENST00000358544.7 | |
VPS13B | NM_152564.5 | c.1782T>C | p.Ile594= | synonymous_variant | 13/62 | ENST00000357162.7 | |
VPS13B | NM_015243.3 | c.1782T>C | p.Ile594= | synonymous_variant | 13/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000358544.7 | c.1782T>C | p.Ile594= | synonymous_variant | 13/62 | 1 | NM_017890.5 | ||
VPS13B | ENST00000357162.7 | c.1782T>C | p.Ile594= | synonymous_variant | 13/62 | 1 | NM_152564.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00631 AC: 961AN: 152180Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00141 AC: 354AN: 251364Hom.: 3 AF XY: 0.00103 AC XY: 140AN XY: 135860
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GnomAD4 exome AF: 0.000578 AC: 845AN: 1461736Hom.: 5 Cov.: 31 AF XY: 0.000481 AC XY: 350AN XY: 727166
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GnomAD4 genome ? AF: 0.00632 AC: 963AN: 152298Hom.: 8 Cov.: 32 AF XY: 0.00628 AC XY: 468AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
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. | Dec 06, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
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