chr8-99106959-G-C

Variant names:

• chr8-99106959-G-C
• rs7818037
• NM_017890.5:c.580+3839G>C

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+3839G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 151,974 control chromosomes in the GnomAD database, including 41,771 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 0.73 (41771 hom., cov: 31)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 1 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=-0.77).
• 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 rank	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.580+3839G>C		intron_variant	Intron 5 of 61	ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.580+3839G>C		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+3839G>C		intron_variant	Intron 5 of 61	1	NM_017890.5	ENSP00000351346.2
VPS13B	ENST00000357162.7	c.580+3839G>C		intron_variant	Intron 5 of 61	1	NM_152564.5	ENSP00000349685.2

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111653 AN: 151856 Hom.: 41766 Cov.: 31

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.841

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.735 AC: 111696 AN: 151974 Hom.: 41771 Cov.: 31 AF XY: 0.733 AC XY: 54446 AN XY: 74282

African (AFR) AF: 0.662 AC: 27410 AN: 41410

American (AMR) AF: 0.605 AC: 9235 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2859 AN: 3470

East Asian (EAS) AF: 0.566 AC: 2927 AN: 5170

South Asian (SAS) AF: 0.866 AC: 4174 AN: 4818

European-Finnish (FIN) AF: 0.793 AC: 8365 AN: 10554

Middle Eastern (MID) AF: 0.846 AC: 247 AN: 292

European-Non Finnish (NFE) AF: 0.797 AC: 54193 AN: 67986

Other (OTH) AF: 0.734 AC: 1545 AN: 2106

Alfa AF: 0.725 Hom.: 2318

Bravo AF: 0.711

Asia WGS AF: 0.685 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		0.25
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: rs7818037; hg19: chr8-100119187; COSMIC: COSV62020961;