Variant 8-99717158-AT-ATT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000357162.7(VPS13B):c.6455-4dup variant causes a splice polypyrimidine tract, 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. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 20 hom., cov: 32)

Exomes 𝑓: 0.012 ( 252 hom. )

Consequence

VPS13B
ENST00000357162.7 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.735

Variant links:

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]

VPS13B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 8-99717158-A-AT is Benign according to our data. Variant chr8-99717158-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 95861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13B	NM_017890.5 linkuse as main transcript	c.6530-4dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5 linkuse as main transcript	c.6455-4dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000357162.7 linkuse as main transcript	c.6455-4dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_152564.5	ENSP00000349685	P1	Q7Z7G8-2
VPS13B	ENST00000358544.7 linkuse as main transcript	c.6530-4dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017890.5	ENSP00000351346		Q7Z7G8-1

Frequencies

GnomAD3 genomes

AF:

0.00892

AC:

1350

AN:

151324

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00925

Gnomad ASJ

AF:

0.00895

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0718

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00885

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.0153

AC:

3482

AN:

227226

Hom.:

AF XY:

0.0186

AC XY:

2291

AN XY:

122912

show subpopulations

Gnomad AFR exome

AF:

0.00144

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.00951

Gnomad EAS exome

AF:

0.000302

Gnomad SAS exome

AF:

0.0661

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0144

GnomAD4 exome

AF:

0.0123

AC:

17321

AN:

1413216

Hom.:

252

Cov.:

AF XY:

0.0138

AC XY:

9747

AN XY:

704632

show subpopulations

Gnomad4 AFR exome

AF:

0.00180

Gnomad4 AMR exome

AF:

0.00504

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.000309

Gnomad4 SAS exome

AF:

0.0635

Gnomad4 FIN exome

AF:

0.0140

Gnomad4 NFE exome

AF:

0.00913

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.00889

AC:

1347

AN:

151442

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

762

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.00160

Gnomad4 AMR

AF:

0.00924

Gnomad4 ASJ

AF:

0.00895

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0712

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.00886

Gnomad4 OTH

AF:

0.00806

Bravo

AF:

0.00652

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Sep 18, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 11, 2013	- -

Cohen syndrome

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2017

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 24, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over