rs10504992

Variant names:

• chr8-99520180-C-T
• rs10504992
• NM_017890.5:c.4709-719C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

VPS13B Gene-Disease associations (from GenCC):

• Cohen syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.4709-719C>T		intron_variant	Intron 29 of 61	ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.4634-719C>T		intron_variant	Intron 29 of 61	ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7	c.4709-719C>T		intron_variant	Intron 29 of 61	1	NM_017890.5	ENSP00000351346.2
VPS13B	ENST00000357162.7	c.4634-719C>T		intron_variant	Intron 29 of 61	1	NM_152564.5	ENSP00000349685.2

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

African (AFR) AF: 0.119 AC: 4906 AN: 41382

American (AMR) AF: 0.0539 AC: 822 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3464

East Asian (EAS) AF: 0.0603 AC: 312 AN: 5176

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4814

European-Finnish (FIN) AF: 0.0447 AC: 471 AN: 10546

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0415 AC: 2819 AN: 67958

Other (OTH) AF: 0.0498 AC: 105 AN: 2108

Alfa AF: 0.0455 Hom.: 105

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
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10504992; hg19: chr8-100532408;