GeneBe

20-58438817-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004738.5(VAPB):​c.316-128G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000334 in 598,784 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

VAPB
NM_004738.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Publications

5 publications found
Variant links:
Genes affected
VAPB (HGNC:12649): (VAMP associated protein B and C) The protein encoded by this gene is a type IV membrane protein found in plasma and intracellular vesicle membranes. The encoded protein is found as a homodimer and as a heterodimer with VAPA. This protein also can interact with VAMP1 and VAMP2 and may be involved in vesicle trafficking. [provided by RefSeq, Jul 2008]
VAPB Gene-Disease associations (from GenCC):
  • amyotrophic lateral sclerosis type 8
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
  • adult-onset proximal spinal muscular atrophy, autosomal dominant
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • amyotrophic lateral sclerosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VAPBNM_004738.5 linkc.316-128G>T intron_variant Intron 3 of 5 ENST00000475243.6 NP_004729.1 O95292-1Q53XM7
VAPBNM_001195677.2 linkc.212-5260G>T intron_variant Intron 2 of 2 NP_001182606.1 O95292-2
VAPBNR_036633.2 linkn.443-2090G>T intron_variant Intron 2 of 3
VAPBXR_001754433.3 linkn.547-128G>T intron_variant Intron 3 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VAPBENST00000475243.6 linkc.316-128G>T intron_variant Intron 3 of 5 1 NM_004738.5 ENSP00000417175.1 O95292-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000334
AC:
2
AN:
598784
Hom.:
0
AF XY:
0.00000313
AC XY:
1
AN XY:
319824
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
14970
American (AMR)
AF:
0.00
AC:
0
AN:
27418
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18598
East Asian (EAS)
AF:
0.00
AC:
0
AN:
32224
South Asian (SAS)
AF:
0.00
AC:
0
AN:
57656
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
35464
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2406
European-Non Finnish (NFE)
AF:
0.00000528
AC:
2
AN:
378712
Other (OTH)
AF:
0.00
AC:
0
AN:
31336
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32
Alfa
AF:
0.00
Hom.:
1315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
15
DANN
Benign
0.51
PhyloP100
1.3
Mutation Taster
=100/0
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

Publications

Other links and lift over

dbSNP: rs2234489; hg19: chr20-57013873; API