rs6991283

Positions:

• chr8-99107735-A-G

Variant summary

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

The NM_017890.5(VPS13B):​c.581-3363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,144 control chromosomes in the GnomAD database, including 52,235 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 0.82 (52235 hom., cov: 31)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.581-3363A>G		intron_variant		ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.581-3363A>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.581-3363A>G		intron_variant		1	NM_152564.5	ENSP00000349685	P1
VPS13B	ENST00000358544.7	c.581-3363A>G		intron_variant		1	NM_017890.5	ENSP00000351346

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125372 AN: 152026 Hom.: 52200 Cov.: 31

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.857

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.825 AC: 125461 AN: 152144 Hom.: 52235 Cov.: 31 AF XY: 0.822 AC XY: 61136 AN XY: 74378

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.801

Alfa AF: 0.824 Hom.: 13926

Bravo AF: 0.807

Asia WGS AF: 0.744 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.40
DANN	Benign	0.43

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: rs6991283; hg19: chr8-100119963;