8-99105893-G-A

Variant names:

• chr8-99105893-G-A
• rs10098153
• NM_017890.5:c.580+2773G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017890.5(VPS13B):​c.580+2773G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,020 control chromosomes in the GnomAD database, including 52,302 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (52302 hom., cov: 30)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Cohen syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.580+2773G>A		intron_variant	Intron 5 of 61	ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.580+2773G>A		intron_variant	Intron 5 of 61	ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7	c.580+2773G>A		intron_variant	Intron 5 of 61	1	NM_017890.5	ENSP00000351346.2
VPS13B	ENST00000357162.7	c.580+2773G>A		intron_variant	Intron 5 of 61	1	NM_152564.5	ENSP00000349685.2

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125392 AN: 151902 Hom.: 52268 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.800

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.825 AC: 125479 AN: 152020 Hom.: 52302 Cov.: 30 AF XY: 0.823 AC XY: 61123 AN XY: 74298

African (AFR) AF: 0.876 AC: 36298 AN: 41438

American (AMR) AF: 0.670 AC: 10222 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2930 AN: 3472

East Asian (EAS) AF: 0.619 AC: 3194 AN: 5162

South Asian (SAS) AF: 0.884 AC: 4258 AN: 4818

European-Finnish (FIN) AF: 0.838 AC: 8855 AN: 10568

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57032 AN: 67994

Other (OTH) AF: 0.801 AC: 1687 AN: 2106

Alfa AF: 0.811 Hom.: 23035

Bravo AF: 0.808

Asia WGS AF: 0.738 AC: 2565 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10098153; hg19: chr8-100118121;