rs2029596

Positions:

• chr8-99318156-A-G
• chr8-99318156-A-T

Variant summary

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

The NM_017890.5(VPS13B):​c.2824+42902A>G 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 152,124 control chromosomes in the GnomAD database, including 41,835 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 0.74 (41835 hom., cov: 33)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.2824+42902A>G		intron_variant		ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.2824+42902A>G		intron_variant		ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000357162.7	c.2824+42902A>G		intron_variant		1	NM_152564.5	ENSP00000349685	P1
VPS13B	ENST00000358544.7	c.2824+42902A>G		intron_variant		1	NM_017890.5	ENSP00000351346

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111769 AN: 152004 Hom.: 41830 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.835

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: 111813 AN: 152124 Hom.: 41835 Cov.: 33 AF XY: 0.733 AC XY: 54499 AN XY: 74384

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.733

Alfa AF: 0.767 Hom.: 5308

Bravo AF: 0.711

Asia WGS AF: 0.685 AC: 2378 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.73

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: rs2029596; hg19: chr8-100330384;