Variant 20-58445517-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_004738.5(VAPB):c.*1282A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 454,294 control chromosomes in the GnomAD database, including 7,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2090 hom., cov: 32)

Exomes 𝑓: 0.17 ( 5060 hom. )

Consequence

VAPB
NM_004738.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.47

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 20-58445517-A-G is Benign according to our data. Variant chr20-58445517-A-G is described in ClinVar as [Benign]. Clinvar id is 338947.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
VAPB	NM_004738.5 linkuse as main transcript	c.*1282A>G	3_prime_UTR_variant	6/6	ENST00000475243.6
VAPB	NM_001195677.2 linkuse as main transcript	c.*1352A>G	3_prime_UTR_variant	3/3
VAPB	NR_036633.2 linkuse as main transcript	n.2060A>G	non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAPB	ENST00000475243.6 linkuse as main transcript	c.*1282A>G		3_prime_UTR_variant	6/6	1	NM_004738.5	P1	O95292-1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23973

AN:

152026

Hom.:

2086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.0827

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.134

GnomAD3 exomes

AF:

0.163

AC:

22236

AN:

136630

Hom.:

2299

AF XY:

0.171

AC XY:

12719

AN XY:

74180

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0563

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.305

Gnomad SAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.168

AC:

50753

AN:

302152

Hom.:

5060

Cov.:

AF XY:

0.179

AC XY:

30767

AN XY:

172210

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.0558

Gnomad4 ASJ exome

AF:

0.172

Gnomad4 EAS exome

AF:

0.317

Gnomad4 SAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.143

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.158

AC:

23983

AN:

152142

Hom.:

2090

Cov.:

AF XY:

0.166

AC XY:

12326

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0825

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.137

Hom.:

672

Bravo

AF:

0.140

Asia WGS

AF:

0.258

AC:

895

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Adult-onset proximal spinal muscular atrophy, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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