20-58389302-AC-A

Position:

• chr20-58389302-AC-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004738.5(VAPB):​c.-149del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 390,658 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0042 (1 hom.)
• Consequence: VAPB NM_004738.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.452

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 20-58389302-AC-A is Benign according to our data. Variant chr20-58389302-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1195499.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAPB	NM_004738.5	c.-149del		5_prime_UTR_variant	1/6	ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.-149del		5_prime_UTR_variant	1/3		NP_001182606.1
VAPB	NR_036633.2	n.83del		non_coding_transcript_exon_variant	1/4
VAPB	XR_001754433.3	n.83del		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243.6	c.-149del		5_prime_UTR_variant	1/6	1	NM_004738.5	ENSP00000417175	P1
VAPB	ENST00000395802.7			upstream_gene_variant		1		ENSP00000379147

Frequencies

GnomAD3 genomes AF: 0.000545 AC: 70 AN: 128488 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000377

Gnomad ASJ AF: 0.000322

Gnomad EAS AF: 0.000490

Gnomad SAS AF: 0.000288

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000577

GnomAD3 exomes AF: 0.00958 AC: 650 AN: 67844 Hom.: 0 AF XY: 0.00923 AC XY: 349 AN XY: 37796

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00583

Gnomad EAS exome AF: 0.0129

Gnomad SAS exome AF: 0.00664

Gnomad FIN exome AF: 0.0131

Gnomad NFE exome AF: 0.00967

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.00422 AC: 1106 AN: 262084 Hom.: 1 Cov.: 5 AF XY: 0.00411 AC XY: 612 AN XY: 148964

Gnomad4 AFR exome AF: 0.00636

Gnomad4 AMR exome AF: 0.00806

Gnomad4 ASJ exome AF: 0.00467

Gnomad4 EAS exome AF: 0.00915

Gnomad4 SAS exome AF: 0.00259

Gnomad4 FIN exome AF: 0.00572

Gnomad4 NFE exome AF: 0.00370

Gnomad4 OTH exome AF: 0.00404

GnomAD4 genome AF: 0.000552 AC: 71 AN: 128574 Hom.: 0 Cov.: 27 AF XY: 0.000534 AC XY: 33 AN XY: 61794

Gnomad4 AFR AF: 0.00114

Gnomad4 AMR AF: 0.000377

Gnomad4 ASJ AF: 0.000322

Gnomad4 EAS AF: 0.000492

Gnomad4 SAS AF: 0.000288

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.000571

Alfa AF: 0.0144 Hom.: 34

Bravo AF: 0.000518

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs546898989; hg19: chr20-56964358;