rs10504991

Variant names:

• chr8-99499055-A-G
• rs10504991
• NM_017890.5:c.3871-2632A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_017890.5(VPS13B):​c.3871-2632A>G variant causes a intron change. The variant allele was found at a frequency of 0.0615 in 152,204 control chromosomes in the GnomAD database, including 398 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 0.062 (398 hom., cov: 32)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.36
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.3871-2632A>G		intron_variant	Intron 25 of 61	ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.3871-2632A>G		intron_variant	Intron 25 of 61	ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7	c.3871-2632A>G		intron_variant	Intron 25 of 61	1	NM_017890.5	ENSP00000351346.2
VPS13B	ENST00000357162.7	c.3871-2632A>G		intron_variant	Intron 25 of 61	1	NM_152564.5	ENSP00000349685.2

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9337 AN: 152086 Hom.: 395 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0503

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

GnomAD4 genome AF: 0.0615 AC: 9364 AN: 152204 Hom.: 398 Cov.: 32 AF XY: 0.0620 AC XY: 4614 AN XY: 74422

African (AFR) AF: 0.113 AC: 4682 AN: 41536

American (AMR) AF: 0.0515 AC: 787 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3470

East Asian (EAS) AF: 0.0605 AC: 314 AN: 5186

South Asian (SAS) AF: 0.0220 AC: 106 AN: 4820

European-Finnish (FIN) AF: 0.0444 AC: 472 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0415 AC: 2822 AN: 67986

Other (OTH) AF: 0.0493 AC: 104 AN: 2110

Alfa AF: 0.0436 Hom.: 305

Bravo AF: 0.0638

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		4.4
Mutation Taster		=98/2	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: rs10504991; hg19: chr8-100511283;