rs3105169

Variant names:

• chr8-99483411-C-A
• rs3105169
• NM_017890.5:c.3870+1609C>A

Variant summary

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

The NM_017890.5(VPS13B):​c.3870+1609C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,030 control chromosomes in the GnomAD database, including 2,830 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 0.17 (2830 hom., cov: 32)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 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.3870+1609C>A		intron	N/A	NP_060360.3
	VPS13B	NM_152564.5	MANE Select	c.3870+1609C>A		intron	N/A	NP_689777.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13B	ENST00000358544.7	TSL:1 MANE Plus Clinical	c.3870+1609C>A		intron	N/A	ENSP00000351346.2
	VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.3870+1609C>A		intron	N/A	ENSP00000349685.2
	VPS13B	ENST00000355155.6	TSL:1	n.3867+1609C>A		intron	N/A	ENSP00000347281.2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26460 AN: 151914 Hom.: 2825 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.174 AC: 26491 AN: 152030 Hom.: 2830 Cov.: 32 AF XY: 0.177 AC XY: 13154 AN XY: 74304

African (AFR) AF: 0.123 AC: 5106 AN: 41482

American (AMR) AF: 0.331 AC: 5047 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1986 AN: 5172

South Asian (SAS) AF: 0.111 AC: 537 AN: 4824

European-Finnish (FIN) AF: 0.163 AC: 1720 AN: 10566

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10933 AN: 67944

Other (OTH) AF: 0.198 AC: 418 AN: 2112

Alfa AF: 0.175 Hom.: 860

Bravo AF: 0.192

Asia WGS AF: 0.255 AC: 885 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.38
DANN	Benign	0.84
PhyloP100		-2.6
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: rs3105169; hg19: chr8-100495639;