NM_017890.5:c.2333+9392C>G

Variant names:

• chr8-99179555-C-G
• rs10808361
• NM_017890.5:c.2333+9392C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017890.5(VPS13B):​c.2333+9392C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,066 control chromosomes in the GnomAD database, including 6,377 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 0.27 (6377 hom., cov: 32)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 3 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017890.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13B	NM_017890.5	MANE Plus Clinical	c.2333+9392C>G		intron	N/A	NP_060360.3
	VPS13B	NM_152564.5	MANE Select	c.2333+9392C>G		intron	N/A	NP_689777.3
	VPS13B	NM_015243.3		c.2333+9392C>G		intron	N/A	NP_056058.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13B	ENST00000358544.7	TSL:1 MANE Plus Clinical	c.2333+9392C>G		intron	N/A	ENSP00000351346.2
	VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.2333+9392C>G		intron	N/A	ENSP00000349685.2
	VPS13B	ENST00000355155.6	TSL:1	n.2333+9392C>G		intron	N/A	ENSP00000347281.2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41632 AN: 151948 Hom.: 6358 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.274 AC: 41703 AN: 152066 Hom.: 6377 Cov.: 32 AF XY: 0.278 AC XY: 20638 AN XY: 74324

African (AFR) AF: 0.340 AC: 14091 AN: 41482

American (AMR) AF: 0.405 AC: 6185 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3472

East Asian (EAS) AF: 0.434 AC: 2251 AN: 5182

South Asian (SAS) AF: 0.208 AC: 1004 AN: 4818

European-Finnish (FIN) AF: 0.221 AC: 2334 AN: 10550

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.212 AC: 14400 AN: 67962

Other (OTH) AF: 0.273 AC: 577 AN: 2110

Alfa AF: 0.239 Hom.: 578

Bravo AF: 0.296

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.31
PhyloP100		-0.39
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: rs10808361; hg19: chr8-100191783;