rs7459833

Variant names:

• chr8-99123903-A-G
• rs7459833
• NM_017890.5:c.1206+2458A>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.1206+2458A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,084 control chromosomes in the GnomAD database, including 40,005 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 0.72 (40005 hom., cov: 31)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.844 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.1206+2458A>G		intron	N/A	NP_060360.3
	VPS13B	NM_152564.5	MANE Select	c.1206+2458A>G		intron	N/A	NP_689777.3
	VPS13B	NM_015243.3		c.1206+2458A>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.1206+2458A>G		intron	N/A	ENSP00000351346.2
	VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.1206+2458A>G		intron	N/A	ENSP00000349685.2
	VPS13B	ENST00000355155.6	TSL:1	n.1206+2458A>G		intron	N/A	ENSP00000347281.2

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108842 AN: 151966 Hom.: 40001 Cov.: 31

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.716 AC: 108874 AN: 152084 Hom.: 40005 Cov.: 31 AF XY: 0.714 AC XY: 53090 AN XY: 74332

African (AFR) AF: 0.595 AC: 24671 AN: 41468

American (AMR) AF: 0.599 AC: 9145 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2861 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2941 AN: 5170

South Asian (SAS) AF: 0.865 AC: 4175 AN: 4824

European-Finnish (FIN) AF: 0.793 AC: 8382 AN: 10570

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54190 AN: 68000

Other (OTH) AF: 0.723 AC: 1530 AN: 2116

Alfa AF: 0.773 Hom.: 54109

Bravo AF: 0.690

Asia WGS AF: 0.681 AC: 2367 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		-0.013
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: rs7459833; hg19: chr8-100136131;