8-99623687-A-G

Position:

• chr8-99623687-A-G

Variant summary

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

The NM_152564.5(VPS13B):​c.5221-18124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,014 control chromosomes in the GnomAD database, including 3,329 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 0.19 (3329 hom., cov: 31)
• Consequence: VPS13B NM_152564.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351

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 (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.5296-18124A>G		intron_variant		ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.5221-18124A>G		intron_variant		ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7	c.5296-18124A>G		intron_variant		1	NM_017890.5	ENSP00000351346.2
VPS13B	ENST00000357162.7	c.5221-18124A>G		intron_variant		1	NM_152564.5	ENSP00000349685.2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28925 AN: 151896 Hom.: 3319 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.191 AC: 28974 AN: 152014 Hom.: 3329 Cov.: 31 AF XY: 0.195 AC XY: 14485 AN XY: 74286

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.193

Alfa AF: 0.169 Hom.: 4980

Bravo AF: 0.210

Asia WGS AF: 0.307 AC: 1069 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	8.3
DANN	Benign	0.75

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: rs4735627; hg19: chr8-100635915;