rs34513504

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017890.5(VPS13B):c.10136+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,591,598 control chromosomes in the GnomAD database, including 27,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5089 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22537 hom. )

Consequence

VPS13B
NM_017890.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.26

Publications

9 publications found

Variant links:

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

VPS13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 8-99848918-G-A is Benign according to our data. Variant chr8-99848918-G-A is described in ClinVar as Benign. ClinVar VariationId is 262652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 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.10136+24G>A		intron	N/A	NP_060360.3
	VPS13B	NM_152564.5	MANE Select	c.10061+24G>A		intron	N/A	NP_689777.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
VPS13B	ENST00000358544.7	TSL:1 MANE Plus Clinical	c.10136+24G>A	intron	N/A	ENSP00000351346.2
VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.10061+24G>A	intron	N/A	ENSP00000349685.2
VPS13B	ENST00000682153.1		n.10136+24G>A	intron	N/A	ENSP00000507923.1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35057

AN:

151900

Hom.:

5062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.196

GnomAD2 exomes

AF:

0.173

AC:

43440

AN:

251094

AF XY:

0.167

show subpopulations

Gnomad AFR exome

AF:

0.419

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.170

AC:

245137

AN:

1439580

Hom.:

22537

Cov.:

AF XY:

0.168

AC XY:

120579

AN XY:

717576

show subpopulations

African (AFR)

AF:

0.422

AC:

13957

AN:

33084

American (AMR)

AF:

0.157

AC:

7029

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

5357

AN:

26006

East Asian (EAS)

AF:

0.122

AC:

4834

AN:

39590

South Asian (SAS)

AF:

0.118

AC:

10111

AN:

85770

European-Finnish (FIN)

AF:

0.146

AC:

7780

AN:

53346

Middle Eastern (MID)

AF:

0.144

AC:

828

AN:

5744

European-Non Finnish (NFE)

AF:

0.169

AC:

184701

AN:

1091762

Other (OTH)

AF:

0.177

AC:

10540

AN:

59588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

9242

18483

27725

36966

46208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6622

13244

19866

26488

33110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.231

AC:

35124

AN:

152018

Hom.:

5089

Cov.:

AF XY:

0.227

AC XY:

16894

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.412

AC:

17080

AN:

41458

American (AMR)

AF:

0.159

AC:

2424

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

719

AN:

3462

East Asian (EAS)

AF:

0.130

AC:

673

AN:

5172

South Asian (SAS)

AF:

0.108

AC:

518

AN:

4814

European-Finnish (FIN)

AF:

0.157

AC:

1661

AN:

10566

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.168

AC:

11447

AN:

67956

Other (OTH)

AF:

0.194

AC:

408

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1296

2592

3888

5184

6480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

654

Bravo

AF:

0.242

Asia WGS

AF:

0.159

AC:

554

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cohen syndrome

Benign:3

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign