chr20-58389302-A-ACC

Position:

• chr20-58389302-A-ACC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004738.5(VAPB):​c.-150_-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 0.0373 in 396,280 control chromosomes in the GnomAD database, including 272 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (231 hom., cov: 27)
  • Exomes 𝑓: 0.028 (41 hom.)
• Consequence: VAPB NM_004738.5 5_prime_UTR
• Clinical Significance: 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 20-58389302-A-ACC is Benign according to our data. Variant chr20-58389302-A-ACC is described in ClinVar as [Benign]. Clinvar id is 1297397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAPB	NM_004738.5	c.-150_-149dup		5_prime_UTR_variant	1/6	ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.-150_-149dup		5_prime_UTR_variant	1/3		NP_001182606.1
VAPB	NR_036633.2	n.82_83dup		non_coding_transcript_exon_variant	1/4
VAPB	XR_001754433.3	n.82_83dup		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243.6	c.-150_-149dup		5_prime_UTR_variant	1/6	1	NM_004738.5	ENSP00000417175	P1
VAPB	ENST00000395802.7			upstream_gene_variant		1		ENSP00000379147

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 7195 AN: 128258 Hom.: 231 Cov.: 27

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.0287

Gnomad EAS AF: 0.00123

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0200

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.0341

GnomAD3 exomes AF: 0.00886 AC: 601 AN: 67844 Hom.: 6 AF XY: 0.00841 AC XY: 318 AN XY: 37796

Gnomad AFR exome AF: 0.00619

Gnomad AMR exome AF: 0.00661

Gnomad ASJ exome AF: 0.00777

Gnomad EAS exome AF: 0.000403

Gnomad SAS exome AF: 0.00227

Gnomad FIN exome AF: 0.0213

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.00982

GnomAD4 exome AF: 0.0284 AC: 7605 AN: 267936 Hom.: 41 Cov.: 5 AF XY: 0.0277 AC XY: 4234 AN XY: 152676

Gnomad4 AFR exome AF: 0.00836

Gnomad4 AMR exome AF: 0.00524

Gnomad4 ASJ exome AF: 0.0105

Gnomad4 EAS exome AF: 0.000132

Gnomad4 SAS exome AF: 0.00726

Gnomad4 FIN exome AF: 0.0505

Gnomad4 NFE exome AF: 0.0410

Gnomad4 OTH exome AF: 0.0283

GnomAD4 genome AF: 0.0560 AC: 7191 AN: 128344 Hom.: 231 Cov.: 27 AF XY: 0.0561 AC XY: 3456 AN XY: 61654

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.0241

Gnomad4 ASJ AF: 0.0287

Gnomad4 EAS AF: 0.000984

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.0337

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;