rs398124337

Positions:

• chr8-99717158-AT-A
• chr8-99717158-AT-ATT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000357162.7(VPS13B):​c.6455-4del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,573,484 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: VPS13B ENST00000357162.7 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.735

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-99717158-AT-A is Benign according to our data. Variant chr8-99717158-AT-A is described in ClinVar as [Benign]. Clinvar id is 1535027.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-99717158-AT-A is described in Lovd as [Benign]. Variant chr8-99717158-AT-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.6530-4del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.6455-4del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000357162.7	c.6455-4del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_152564.5	ENSP00000349685	P1
VPS13B	ENST00000358544.7	c.6530-4del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017890.5	ENSP00000351346

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151326 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000795 AC: 113 AN: 1422040 Hom.: 0 Cov.: 30 AF XY: 0.0000790 AC XY: 56 AN XY: 708722

Gnomad4 AFR exome AF: 0.0000923

Gnomad4 AMR exome AF: 0.0000453

Gnomad4 ASJ exome AF: 0.0000391

Gnomad4 EAS exome AF: 0.000205

Gnomad4 SAS exome AF: 0.0000469

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.0000816

Gnomad4 OTH exome AF: 0.000102

GnomAD4 genome AF: 0.0000396 AC: 6 AN: 151444 Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 4 AN XY: 74002

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.0000660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000227

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cohen syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs398124337; hg19: chr8-100729386;