Variant rs2234487 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000475243.6(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
ENST00000475243.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.731

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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	MANE	Protein
VAPB	NM_004738.5 linkuse as main transcript	c.315+35C>T	intron_variant	ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2 linkuse as main transcript	c.212-9337C>T	intron_variant		NP_001182606.1
VAPB	NR_036633.2 linkuse as main transcript	n.443-6167C>T	intron_variant, non_coding_transcript_variant
VAPB	XR_001754433.3 linkuse as main transcript	n.546+35C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243.6 linkuse as main transcript	c.315+35C>T		intron_variant		1	NM_004738.5	ENSP00000417175	P1	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

GnomAD3 exomes

AF:

0.413

AC:

99828

AN:

241560

Hom.:

21416

AF XY:

0.416

AC XY:

54425

AN XY:

130956

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 SAS exome

AF:

0.363

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

Gnomad4 AFR exome

AF:

0.420

Gnomad4 AMR exome

AF:

0.309

Gnomad4 ASJ exome

AF:

0.410

Gnomad4 EAS exome

AF:

0.631

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.518

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.431

AC:

65409

AN:

151754

Hom.:

14311

Cov.:

AF XY:

0.437

AC XY:

32416

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.428

Gnomad4 AMR

AF:

0.367

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.586

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.549

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.400

Alfa

AF:

0.427

Hom.:

2601

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Amyotrophic lateral sclerosis type 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Adult-onset proximal spinal muscular atrophy, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.4

DANN

Benign

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over