Variant rs34513504 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152564.5(VPS13B):c.10061+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,591,598 control chromosomes in the GnomAD database, including 27,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5089 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22537 hom. )

Consequence

VPS13B
NM_152564.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.26

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 8-99848918-G-A is Benign according to our data. Variant chr8-99848918-G-A is described in ClinVar as [Benign]. Clinvar id is 262652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-99848918-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13B	NM_017890.5 link	c.10136+24G>A		intron_variant		ENST00000358544.7	NP_060360.3	Q7Z7G8-1
VPS13B	NM_152564.5 link	c.10061+24G>A		intron_variant		ENST00000357162.7	NP_689777.3	Q7Z7G8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7 link	c.10136+24G>A		intron_variant		1	NM_017890.5	ENSP00000351346.2		Q7Z7G8-1
VPS13B	ENST00000357162.7 link	c.10061+24G>A		intron_variant		1	NM_152564.5	ENSP00000349685.2		Q7Z7G8-2

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35057

AN:

151900

Hom.:

5062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.173

AC:

43440

AN:

251094

Hom.:

4423

AF XY:

0.167

AC XY:

22675

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.419

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.131

Gnomad SAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.170

AC:

245137

AN:

1439580

Hom.:

22537

Cov.:

AF XY:

0.168

AC XY:

120579

AN XY:

717576

show subpopulations

Gnomad4 AFR exome

AF:

0.422

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.206

Gnomad4 EAS exome

AF:

0.122

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.231

AC:

35124

AN:

152018

Hom.:

5089

Cov.:

AF XY:

0.227

AC XY:

16894

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.412

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.130

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.168

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.195

Hom.:

654

Bravo

AF:

0.242

Asia WGS

AF:

0.159

AC:

554

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cohen syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.029

DANN

Benign

0.18

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