chr8-99720960-A-G

Position:

chr8-99720960-A-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_152564.5(VPS13B):c.6963A>G(p.Val2321Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 1,613,908 control chromosomes in the GnomAD database, including 2,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 537 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1688 hom. )

Consequence

VPS13B
NM_152564.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.618

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:

VPS13B (HGNC:):

VPS13B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 8-99720960-A-G is Benign according to our data. Variant chr8-99720960-A-G is described in ClinVar as [Benign]. Clinvar id is 95863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-99720960-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.618 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 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.7038A>G	p.Val2346Val	synonymous_variant	39/62	ENST00000358544.7	NP_060360.3	Q7Z7G8-1
VPS13B	NM_152564.5 linkuse as main transcript	c.6963A>G	p.Val2321Val	synonymous_variant	39/62	ENST00000357162.7	NP_689777.3	Q7Z7G8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7 linkuse as main transcript	c.7038A>G	p.Val2346Val	synonymous_variant	39/62	1	NM_017890.5	ENSP00000351346.2		Q7Z7G8-1
VPS13B	ENST00000357162.7 linkuse as main transcript	c.6963A>G	p.Val2321Val	synonymous_variant	39/62	1	NM_152564.5	ENSP00000349685.2		Q7Z7G8-2

Frequencies

GnomAD3 genomes

AF:

0.0686

AC:

10428

AN:

152056

Hom.:

534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0502

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.0445

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0416

Gnomad OTH

AF:

0.0580

GnomAD3 exomes

AF:

0.0474

AC:

11903

AN:

251248

Hom.:

404

AF XY:

0.0441

AC XY:

5982

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0560

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.0633

Gnomad SAS exome

AF:

0.0227

Gnomad FIN exome

AF:

0.0453

Gnomad NFE exome

AF:

0.0391

Gnomad OTH exome

AF:

0.0390

GnomAD4 exome

AF:

0.0444

AC:

64955

AN:

1461734

Hom.:

1688

Cov.:

AF XY:

0.0431

AC XY:

31322

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.0548

Gnomad4 ASJ exome

AF:

0.0183

Gnomad4 EAS exome

AF:

0.0449

Gnomad4 SAS exome

AF:

0.0231

Gnomad4 FIN exome

AF:

0.0423

Gnomad4 NFE exome

AF:

0.0434

Gnomad4 OTH exome

AF:

0.0471

GnomAD4 genome

AF:

0.0687

AC:

10457

AN:

152174

Hom.:

537

Cov.:

AF XY:

0.0688

AC XY:

5120

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.0503

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.0565

Gnomad4 SAS

AF:

0.0222

Gnomad4 FIN

AF:

0.0445

Gnomad4 NFE

AF:

0.0416

Gnomad4 OTH

AF:

0.0569

Alfa

AF:

0.0555

Hom.:

138

Bravo

AF:

0.0727

Asia WGS

AF:

0.0560

AC:

197

AN:

3476

EpiCase

AF:

0.0386

EpiControl

AF:

0.0348

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 02, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 16, 2022	- -

Cohen syndrome

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -
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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
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. -

not provided

Benign:2

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

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2016

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

5.5

DANN

Benign

0.74

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