rs118061300

Variant names:

• chr8-99819365-C-T
• rs118061300
• NM_017890.5:c.8697-47C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017890.5(VPS13B):​c.8697-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,600,524 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (54 hom.)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.634
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 8-99819365-C-T is Benign according to our data. Variant chr8-99819365-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 262665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00557 (848/152246) while in subpopulation NFE AF = 0.00916 (623/68016). AF 95% confidence interval is 0.00856. There are 6 homozygotes in GnomAd4. There are 393 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.8697-47C>T		intron	N/A	NP_060360.3
	VPS13B	NM_152564.5	MANE Select	c.8622-47C>T		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.8697-47C>T		intron	N/A	ENSP00000351346.2
	VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.8622-47C>T		intron	N/A	ENSP00000349685.2
	VPS13B	ENST00000682153.1		n.8697-47C>T		intron	N/A	ENSP00000507923.1

Frequencies

GnomAD3 genomes AF: 0.00557 AC: 848 AN: 152128 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00916

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00497 AC: 1230 AN: 247482 AF XY: 0.00483

Gnomad AFR exome AF: 0.00118

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00309

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00827

Gnomad NFE exome AF: 0.00809

Gnomad OTH exome AF: 0.00417

GnomAD4 exome AF: 0.00758 AC: 10983 AN: 1448278 Hom.: 54 Cov.: 29 AF XY: 0.00739 AC XY: 5329 AN XY: 721432

African (AFR) AF: 0.000786 AC: 26 AN: 33074

American (AMR) AF: 0.00130 AC: 58 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00338 AC: 88 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39414

South Asian (SAS) AF: 0.000629 AC: 54 AN: 85886

European-Finnish (FIN) AF: 0.00929 AC: 493 AN: 53070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00903 AC: 9937 AN: 1100556

Other (OTH) AF: 0.00546 AC: 327 AN: 59918

GnomAD4 genome AF: 0.00557 AC: 848 AN: 152246 Hom.: 6 Cov.: 32 AF XY: 0.00528 AC XY: 393 AN XY: 74458

African (AFR) AF: 0.00113 AC: 47 AN: 41536

American (AMR) AF: 0.00137 AC: 21 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.0112 AC: 119 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00916 AC: 623 AN: 68016

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00774 Hom.: 4

Bravo AF: 0.00465

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.67
PhyloP100		0.63
Mutation Taster		=99/1	polymorphism

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: rs118061300; hg19: chr8-100831593;