Variant 20-58389302-A-AC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004738.5(VAPB):c.-149dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 395,364 control chromosomes in the GnomAD database, including 2,062 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1920 hom., cov: 27)

Exomes 𝑓: 0.067 ( 142 hom. )

Consequence

VAPB
NM_004738.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.452

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 -16 ACMG points.

BP6

Variant 20-58389302-A-AC is Benign according to our data. Variant chr20-58389302-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 338925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
VAPB	NM_004738.5 linkuse as main transcript	c.-149dup	5_prime_UTR_variant	1/6	ENST00000475243.6
VAPB	NM_001195677.2 linkuse as main transcript	c.-149dup	5_prime_UTR_variant	1/3
VAPB	NR_036633.2 linkuse as main transcript	n.83dup	non_coding_transcript_exon_variant	1/4
VAPB	XR_001754433.3 linkuse as main transcript	n.83dup	non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAPB	ENST00000475243.6 linkuse as main transcript	c.-149dup		5_prime_UTR_variant	1/6	1	NM_004738.5	P1	O95292-1
VAPB	ENST00000395802.7 linkuse as main transcript			upstream_gene_variant		1			O95292-2

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

19399

AN:

128310

Hom.:

1919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.0797

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0157

Gnomad SAS

AF:

0.0847

Gnomad FIN

AF:

0.0536

Gnomad MID

AF:

0.100

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.146

GnomAD3 exomes

AF:

0.0601

AC:

4078

AN:

67844

Hom.:

AF XY:

0.0613

AC XY:

2317

AN XY:

37796

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.0536

Gnomad ASJ exome

AF:

0.0749

Gnomad EAS exome

AF:

0.0163

Gnomad SAS exome

AF:

0.0488

Gnomad FIN exome

AF:

0.0402

Gnomad NFE exome

AF:

0.0737

Gnomad OTH exome

AF:

0.0673

GnomAD4 exome

AF:

0.0669

AC:

17869

AN:

266966

Hom.:

142

Cov.:

AF XY:

0.0681

AC XY:

10352

AN XY:

151902

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0398

Gnomad4 ASJ exome

AF:

0.0639

Gnomad4 EAS exome

AF:

0.00598

Gnomad4 SAS exome

AF:

0.0589

Gnomad4 FIN exome

AF:

0.0352

Gnomad4 NFE exome

AF:

0.0779

Gnomad4 OTH exome

AF:

0.0750

GnomAD4 genome

AF:

0.151

AC:

19413

AN:

128398

Hom.:

1920

Cov.:

AF XY:

0.148

AC XY:

9151

AN XY:

61718

show subpopulations

Gnomad4 AFR

AF:

0.299

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0155

Gnomad4 SAS

AF:

0.0842

Gnomad4 FIN

AF:

0.0536

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.145

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Amyotrophic Lateral Sclerosis, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 29, 2019

- -

Spinal Muscular Atrophy, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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