rs2234487

Variant names:

Variant summary

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

The NM_004738.5(VAPB):c.315+35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,041,992 control chromosomes in the GnomAD database, including 92,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14311 hom., cov: 32)

Exomes 𝑓: 0.41 ( 78654 hom. )

Consequence

VAPB
NM_004738.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.731

Publications

14 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

VAPB 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=-0.53).

BP6

Variant 20-58434740-C-T is Benign according to our data. Variant chr20-58434740-C-T is described in ClinVar as Benign. ClinVar VariationId is 259537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
VAPB	NM_004738.5 link	c.315+35C>T	intron_variant	Intron 3 of 5	ENST00000475243.6	NP_004729.1	O95292-1Q53XM7
VAPB	NM_001195677.2 link	c.212-9337C>T	intron_variant	Intron 2 of 2		NP_001182606.1	O95292-2
VAPB	NR_036633.2 link	n.443-6167C>T	intron_variant	Intron 2 of 3
VAPB	XR_001754433.3 link	n.546+35C>T	intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243.6 link	c.315+35C>T		intron_variant	Intron 3 of 5	1	NM_004738.5	ENSP00000417175.1		O95292-1

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65360

AN:

151634

Hom.:

14302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.586

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.396

GnomAD2 exomes

AF:

0.413

AC:

99828

AN:

241560

AF XY:

0.416

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.302

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.572

Gnomad FIN exome

AF:

0.531

Gnomad NFE exome

AF:

0.415

Gnomad OTH exome

AF:

0.402

GnomAD4 exome

AF:

0.411

AC:

365532

AN:

890238

Hom.:

78654

Cov.:

AF XY:

0.411

AC XY:

191803

AN XY:

466374

show subpopulations

African (AFR)

AF:

0.420

AC:

9392

AN:

22374

American (AMR)

AF:

0.309

AC:

13484

AN:

43618

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

9295

AN:

22664

East Asian (EAS)

AF:

0.631

AC:

23234

AN:

36830

South Asian (SAS)

AF:

0.359

AC:

26686

AN:

74306

European-Finnish (FIN)

AF:

0.518

AC:

25469

AN:

49148

Middle Eastern (MID)

AF:

0.409

AC:

1757

AN:

4296

European-Non Finnish (NFE)

AF:

0.402

AC:

239370

AN:

595422

Other (OTH)

AF:

0.405

AC:

16845

AN:

41580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

9762

19524

29287

39049

48811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4860

9720

14580

19440

24300

<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:

0.431

AC:

65409

AN:

151754

Hom.:

14311

Cov.:

AF XY:

0.437

AC XY:

32416

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.428

AC:

17705

AN:

41346

American (AMR)

AF:

0.367

AC:

5588

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1452

AN:

3468

East Asian (EAS)

AF:

0.586

AC:

3033

AN:

5180

South Asian (SAS)

AF:

0.358

AC:

1721

AN:

4806

European-Finnish (FIN)

AF:

0.549

AC:

5764

AN:

10494

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28755

AN:

67912

Other (OTH)

AF:

0.400

AC:

843

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1907

3815

5722

7630

9537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.428

Hom.:

2676

Bravo

AF:

0.413

Asia WGS

AF:

0.452

AC:

1567

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amyotrophic lateral sclerosis type 8

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Adult-onset proximal spinal muscular atrophy, autosomal dominant

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.4

(source)

DANN

Benign

0.73

PhyloP100

0.73

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over