rs2442756

Variant names:

• chr8-99816910-A-C
• rs2442756
• NM_017890.5:c.8173-630A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-99816910-A-C
• chr8-99816910-A-G
• chr8-99816910-A-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.8173-630A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,988 control chromosomes in the GnomAD database, including 10,533 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 0.37 (10533 hom., cov: 31)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.8173-630A>C		intron_variant	Intron 44 of 61	ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.8098-630A>C		intron_variant	Intron 44 of 61	ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7	c.8173-630A>C		intron_variant	Intron 44 of 61	1	NM_017890.5	ENSP00000351346.2
VPS13B	ENST00000357162.7	c.8098-630A>C		intron_variant	Intron 44 of 61	1	NM_152564.5	ENSP00000349685.2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56009 AN: 151870 Hom.: 10520 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.369 AC: 56061 AN: 151988 Hom.: 10533 Cov.: 31 AF XY: 0.370 AC XY: 27490 AN XY: 74290

African (AFR) AF: 0.372 AC: 15408 AN: 41444

American (AMR) AF: 0.461 AC: 7043 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2447 AN: 5172

South Asian (SAS) AF: 0.275 AC: 1323 AN: 4814

European-Finnish (FIN) AF: 0.334 AC: 3524 AN: 10552

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24010 AN: 67956

Other (OTH) AF: 0.345 AC: 727 AN: 2110

Alfa AF: 0.357 Hom.: 40908

Bravo AF: 0.386

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.90
PhyloP100		-1.9
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: rs2442756; hg19: chr8-100829138;