rs72676269

chr8-99859513-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_017890.5(VPS13B):c.11119+33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,595,412 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (8 hom., cov: 32)
  • Exomes 𝑓: 0.012 (131 hom.)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.05

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-99859513-C-A is Benign according to our data. Variant chr8-99859513-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 262654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-99859513-C-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13B	NM_017890.5	c.11119+33C>A		intron_variant		ENST00000358544.7
VPS13B	NM_152564.5	c.11044+33C>A		intron_variant		ENST00000357162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13B	ENST00000357162.7	c.11044+33C>A		intron_variant		1	NM_152564.5	P1
VPS13B	ENST00000358544.7	c.11119+33C>A		intron_variant		1	NM_017890.5

Frequencies

GnomAD3 genomes AF: 0.00789 AC: 1186 AN: 150296 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00277

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00418

Gnomad ASJ AF: 0.00232

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.00724

GnomAD3 exomes AF: 0.00877 AC: 2016 AN: 229860 Hom.: 8 AF XY: 0.00878 AC XY: 1105 AN XY: 125836

Gnomad AFR exome AF: 0.00332

Gnomad AMR exome AF: 0.00377

Gnomad ASJ exome AF: 0.00290

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00234

Gnomad FIN exome AF: 0.0163

Gnomad NFE exome AF: 0.0138

Gnomad OTH exome AF: 0.00646

GnomAD4 exome AF: 0.0118 AC: 17101 AN: 1445004 Hom.: 131 Cov.: 32 AF XY: 0.0116 AC XY: 8325 AN XY: 719376

Gnomad4 AFR exome AF: 0.00253

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.00289

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00233

Gnomad4 FIN exome AF: 0.0138

Gnomad4 NFE exome AF: 0.0140

Gnomad4 OTH exome AF: 0.00852

GnomAD4 genome AF: 0.00788 AC: 1185 AN: 150408 Hom.: 8 Cov.: 32 AF XY: 0.00771 AC XY: 566 AN XY: 73394

Gnomad4 AFR AF: 0.00276

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.00232

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00168

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.00716

Alfa AF: 0.00840 Hom.: 1

Bravo AF: 0.00656

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.050
Dann	Benign	0.64

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: rs72676269; hg19: chr8-100871741;