rs10504992

Positions:

• chr8-99520180-C-T

Variant summary

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

The NM_017890.5(VPS13B):​c.4709-719C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 151,912 control chromosomes in the GnomAD database, including 410 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 0.063 (410 hom., cov: 31)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13B	NM_017890.5	c.4709-719C>T		intron_variant		ENST00000358544.7
VPS13B	NM_152564.5	c.4634-719C>T		intron_variant		ENST00000357162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13B	ENST00000357162.7	c.4634-719C>T		intron_variant		1	NM_152564.5	P1
VPS13B	ENST00000358544.7	c.4709-719C>T		intron_variant		1	NM_017890.5

Frequencies

GnomAD3 genomes AF: 0.0632 AC: 9595 AN: 151794 Hom.: 405 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0447

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0508

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

GnomAD4 genome AF: 0.0633 AC: 9619 AN: 151912 Hom.: 410 Cov.: 31 AF XY: 0.0637 AC XY: 4725 AN XY: 74226

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0539

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.0603

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0447

Gnomad4 NFE AF: 0.0415

Gnomad4 OTH AF: 0.0498

Alfa AF: 0.0448 Hom.: 90

Bravo AF: 0.0663

Asia WGS AF: 0.0580 AC: 203 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.72

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: rs10504992; hg19: chr8-100532408;