rs10504991

chr8-99499055-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
VPS13B	NM_017890.5	c.3871-2632A>G		intron_variant		ENST00000358544.7
VPS13B	NM_152564.5	c.3871-2632A>G		intron_variant		ENST00000357162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13B	ENST00000357162.7	c.3871-2632A>G		intron_variant		1	NM_152564.5	P1
VPS13B	ENST00000358544.7	c.3871-2632A>G		intron_variant		1	NM_017890.5

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

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.0605

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0444

Gnomad4 NFE AF: 0.0415

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0413 Hom.: 224

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

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: rs10504991; hg19: chr8-100511283;