rs34513504

chr8-99848918-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017890.5(VPS13B):c.10136+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_017890.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.26

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]

ACMG classification

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	UniProt
VPS13B	NM_017890.5	c.10136+24G>A		intron_variant		ENST00000358544.7
VPS13B	NM_152564.5	c.10061+24G>A		intron_variant		ENST00000357162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13B	ENST00000357162.7	c.10061+24G>A		intron_variant		1	NM_152564.5	P1
VPS13B	ENST00000358544.7	c.10136+24G>A		intron_variant		1	NM_017890.5

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35057 AN: 151900 Hom.: 5062 Cov.: 32

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

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.: 26 AF XY: 0.168 AC XY: 120579 AN XY: 717576

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.: 32 AF XY: 0.227 AC XY: 16894 AN XY: 74314

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cohen syndrome Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 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	Genome-Nilou Lab	Jul 01, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

Other links and lift over

dbSNP: rs34513504; hg19: chr8-100861146; COSMIC: COSV62132342;