rs3105169

Positions:

• chr8-99483411-C-A

Variant summary

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

The NM_017890.5(VPS13B):​c.3870+1609C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,030 control chromosomes in the GnomAD database, including 2,830 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 0.17 (2830 hom., cov: 32)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13B	NM_017890.5	c.3870+1609C>A		intron_variant		ENST00000358544.7
VPS13B	NM_152564.5	c.3870+1609C>A		intron_variant		ENST00000357162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13B	ENST00000357162.7	c.3870+1609C>A		intron_variant		1	NM_152564.5	P1
VPS13B	ENST00000358544.7	c.3870+1609C>A		intron_variant		1	NM_017890.5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26460 AN: 151914 Hom.: 2825 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.174 AC: 26491 AN: 152030 Hom.: 2830 Cov.: 32 AF XY: 0.177 AC XY: 13154 AN XY: 74304

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.198

Alfa AF: 0.158 Hom.: 317

Bravo AF: 0.192

Asia WGS AF: 0.255 AC: 885 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.38
DANN	Benign	0.84

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: rs3105169; hg19: chr8-100495639;