rs10808361

Positions:

• chr8-99179555-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017890.5(VPS13B):​c.2333+9392C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,066 control chromosomes in the GnomAD database, including 6,377 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 0.27 (6377 hom., cov: 32)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.2333+9392C>G		intron_variant		ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.2333+9392C>G		intron_variant		ENST00000357162.7	NP_689777.3
VPS13B	NM_015243.3	c.2333+9392C>G		intron_variant			NP_056058.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000357162.7	c.2333+9392C>G		intron_variant		1	NM_152564.5	ENSP00000349685	P1
VPS13B	ENST00000358544.7	c.2333+9392C>G		intron_variant		1	NM_017890.5	ENSP00000351346

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41632 AN: 151948 Hom.: 6358 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.274 AC: 41703 AN: 152066 Hom.: 6377 Cov.: 32 AF XY: 0.278 AC XY: 20638 AN XY: 74324

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.273

Alfa AF: 0.239 Hom.: 578

Bravo AF: 0.296

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.31

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: rs10808361; hg19: chr8-100191783;