8-99121478-T-G

Position:

chr8-99121478-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The NM_181661.3(VPS13B):c.1239T>G(p.Tyr413*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 1,610,834 control chromosomes in the GnomAD database, including 490,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42338 hom., cov: 32)

Exomes 𝑓: 0.78 ( 448444 hom. )

Consequence

VPS13B
NM_181661.3 stop_gained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.239

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 -14 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00721 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 8-99121478-T-G is Benign according to our data. Variant chr8-99121478-T-G is described in ClinVar as [Benign]. Clinvar id is 262657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-99121478-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.844 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.1206+33T>G		intron_variant		ENST00000358544.7	NP_060360.3	Q7Z7G8-1
VPS13B	NM_152564.5 linkuse as main transcript	c.1206+33T>G		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 linkuse as main transcript	c.1206+33T>G		intron_variant		1	NM_017890.5	ENSP00000351346.2		Q7Z7G8-1
VPS13B	ENST00000357162.7 linkuse as main transcript	c.1206+33T>G		intron_variant		1	NM_152564.5	ENSP00000349685.2		Q7Z7G8-2

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112575

AN:

151944

Hom.:

42332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.866

Gnomad FIN

AF:

0.785

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.797

Gnomad OTH

AF:

0.735

GnomAD3 exomes

AF:

0.739

AC:

183487

AN:

248432

Hom.:

69764

AF XY:

0.756

AC XY:

101577

AN XY:

134340

show subpopulations

Gnomad AFR exome

AF:

0.685

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.817

Gnomad EAS exome

AF:

0.546

Gnomad SAS exome

AF:

0.871

Gnomad FIN exome

AF:

0.780

Gnomad NFE exome

AF:

0.798

Gnomad OTH exome

AF:

0.752

GnomAD4 exome

AF:

0.781

AC:

1139503

AN:

1458772

Hom.:

448444

Cov.:

AF XY:

0.785

AC XY:

569785

AN XY:

725430

show subpopulations

Gnomad4 AFR exome

AF:

0.682

Gnomad4 AMR exome

AF:

0.519

Gnomad4 ASJ exome

AF:

0.819

Gnomad4 EAS exome

AF:

0.586

Gnomad4 SAS exome

AF:

0.871

Gnomad4 FIN exome

AF:

0.789

Gnomad4 NFE exome

AF:

0.793

Gnomad4 OTH exome

AF:

0.776

GnomAD4 genome

AF:

0.741

AC:

112622

AN:

152062

Hom.:

42338

Cov.:

AF XY:

0.738

AC XY:

54870

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.684

Gnomad4 AMR

AF:

0.608

Gnomad4 ASJ

AF:

0.824

Gnomad4 EAS

AF:

0.569

Gnomad4 SAS

AF:

0.866

Gnomad4 FIN

AF:

0.785

Gnomad4 NFE

AF:

0.797

Gnomad4 OTH

AF:

0.738

Alfa

AF:

0.783

Hom.:

80368

Bravo

AF:

0.718

TwinsUK

AF:

0.809

AC:

2999

ALSPAC

AF:

0.803

AC:

3095

ESP6500AA

AF:

0.681

AC:

3001

ESP6500EA

AF:

0.794

AC:

6827

ExAC

AF:

0.749

AC:

90921

Asia WGS

AF:

0.686

AC:

2384

AN:

3478

EpiCase

AF:

0.792

EpiControl

AF:

0.798

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cohen syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jul 02, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 08, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

DANN

Benign

0.87

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.12

Vest4

0.044

GERP RS

3.3

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