NM_017890.5:c.3871-2934G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017890.5(VPS13B):​c.3871-2934G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 152,082 control chromosomes in the GnomAD database, including 449 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 0.065 ( 449 hom., cov: 32)

Consequence

VPS13B
NM_017890.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63

Publications

2 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS13BNM_017890.5 linkc.3871-2934G>C intron_variant Intron 25 of 61 ENST00000358544.7 NP_060360.3 Q7Z7G8-1
VPS13BNM_152564.5 linkc.3871-2934G>C intron_variant Intron 25 of 61 ENST00000357162.7 NP_689777.3 Q7Z7G8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VPS13BENST00000358544.7 linkc.3871-2934G>C intron_variant Intron 25 of 61 1 NM_017890.5 ENSP00000351346.2 Q7Z7G8-1
VPS13BENST00000357162.7 linkc.3871-2934G>C intron_variant Intron 25 of 61 1 NM_152564.5 ENSP00000349685.2 Q7Z7G8-2

Frequencies

GnomAD3 genomes
AF:
0.0651
AC:
9895
AN:
151962
Hom.:
444
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.125
Gnomad AMI
AF:
0.00987
Gnomad AMR
AF:
0.0551
Gnomad ASJ
AF:
0.0179
Gnomad EAS
AF:
0.0607
Gnomad SAS
AF:
0.0217
Gnomad FIN
AF:
0.0445
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.0414
Gnomad OTH
AF:
0.0522
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0653
AC:
9926
AN:
152082
Hom.:
449
Cov.:
32
AF XY:
0.0656
AC XY:
4876
AN XY:
74362
show subpopulations
African (AFR)
AF:
0.125
AC:
5197
AN:
41484
American (AMR)
AF:
0.0551
AC:
841
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.0179
AC:
62
AN:
3470
East Asian (EAS)
AF:
0.0606
AC:
314
AN:
5180
South Asian (SAS)
AF:
0.0218
AC:
105
AN:
4826
European-Finnish (FIN)
AF:
0.0445
AC:
471
AN:
10588
Middle Eastern (MID)
AF:
0.0238
AC:
7
AN:
294
European-Non Finnish (NFE)
AF:
0.0414
AC:
2812
AN:
67960
Other (OTH)
AF:
0.0512
AC:
108
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
462
924
1385
1847
2309
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
108
216
324
432
540
<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:
0.0545
Hom.:
34
Bravo
AF:
0.0684
Asia WGS
AF:
0.0570
AC:
201
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
14
DANN
Benign
0.66
PhyloP100
1.6
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

Publications

Other links and lift over

dbSNP: rs10504990; hg19: chr8-100510981; API