chr8-99717158-A-AT
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_152564.5(VPS13B):c.6455-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,564,658 control chromosomes in the GnomAD database, including 272 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_152564.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS13B | NM_017890.5 | c.6530-4dupT | splice_region_variant, intron_variant | Intron 36 of 61 | ENST00000358544.7 | NP_060360.3 | ||
VPS13B | NM_152564.5 | c.6455-4dupT | splice_region_variant, intron_variant | Intron 36 of 61 | ENST00000357162.7 | NP_689777.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS13B | ENST00000358544.7 | c.6530-13_6530-12insT | intron_variant | Intron 36 of 61 | 1 | NM_017890.5 | ENSP00000351346.2 | |||
VPS13B | ENST00000357162.7 | c.6455-13_6455-12insT | intron_variant | Intron 36 of 61 | 1 | NM_152564.5 | ENSP00000349685.2 |
Frequencies
GnomAD3 genomes AF: 0.00892 AC: 1350AN: 151324Hom.: 22 Cov.: 32
GnomAD3 exomes AF: 0.0153 AC: 3482AN: 227226Hom.: 92 AF XY: 0.0186 AC XY: 2291AN XY: 122912
GnomAD4 exome AF: 0.0123 AC: 17321AN: 1413216Hom.: 252 Cov.: 30 AF XY: 0.0138 AC XY: 9747AN XY: 704632
GnomAD4 genome AF: 0.00889 AC: 1347AN: 151442Hom.: 20 Cov.: 32 AF XY: 0.0103 AC XY: 762AN XY: 74004
ClinVar
Submissions by phenotype
not specified Benign:2
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Variant summary: c.6530-4dupT in VPS13B gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect a normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.01956 (1930/98690 chrs tested, including 49 homozygotes), predominantly in individuals of South Asian descent (0.068; 1002/14612 chrs tested). The observed frequency greatly exceeds the maximum expected allele frequency for a pathogenic variant of 0.0025, suggesting that it is likely to be a common polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but is cited as Likely Benign/Benign by reputable database/clinical laboratory. Taking together, the variant was classified as Benign. -
Cohen syndrome Benign:2
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Inborn genetic diseases Benign:1
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. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at