chr8-99822954-T-C

Variant names:

• chr8-99822954-T-C
• rs959695
• NM_017890.5:c.9259-878T>C

Variant summary

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

The NM_017890.5(VPS13B):​c.9259-878T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,898 control chromosomes in the GnomAD database, including 11,158 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 0.38 (11158 hom., cov: 32)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 7 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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.9259-878T>C		intron_variant	Intron 50 of 61	ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.9184-878T>C		intron_variant	Intron 50 of 61	ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7	c.9259-878T>C		intron_variant	Intron 50 of 61	1	NM_017890.5	ENSP00000351346.2
VPS13B	ENST00000357162.7	c.9184-878T>C		intron_variant	Intron 50 of 61	1	NM_152564.5	ENSP00000349685.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57619 AN: 151780 Hom.: 11148 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.380 AC: 57668 AN: 151898 Hom.: 11158 Cov.: 32 AF XY: 0.381 AC XY: 28266 AN XY: 74246

African (AFR) AF: 0.410 AC: 16985 AN: 41412

American (AMR) AF: 0.464 AC: 7071 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2434 AN: 5164

South Asian (SAS) AF: 0.280 AC: 1346 AN: 4806

European-Finnish (FIN) AF: 0.331 AC: 3492 AN: 10546

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23996 AN: 67950

Other (OTH) AF: 0.352 AC: 743 AN: 2110

Alfa AF: 0.351 Hom.: 1207

Bravo AF: 0.399

Asia WGS AF: 0.395 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		1.5
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: rs959695; hg19: chr8-100835182; COSMIC: COSV62159169;