rs2234489

Positions:

• chr20-58438817-G-A
• chr20-58438817-G-C
• chr20-58438817-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004738.5(VAPB):​c.316-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 750,374 control chromosomes in the GnomAD database, including 12,771 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2680 hom., cov: 32)
  • Exomes 𝑓: 0.17 (10091 hom.)
• Consequence: VAPB NM_004738.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 20-58438817-G-A is Benign according to our data. Variant chr20-58438817-G-A is described in ClinVar as [Benign]. Clinvar id is 1181952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAPB	NM_004738.5	c.316-128G>A		intron_variant		ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.212-5260G>A		intron_variant			NP_001182606.1
VAPB	NR_036633.2	n.443-2090G>A		intron_variant
VAPB	XR_001754433.3	n.547-128G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243.6	c.316-128G>A		intron_variant		1	NM_004738.5	ENSP00000417175.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27189 AN: 152058 Hom.: 2675 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.169 AC: 101301 AN: 598198 Hom.: 10091 AF XY: 0.174 AC XY: 55473 AN XY: 319480

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.0641

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.179 AC: 27210 AN: 152176 Hom.: 2680 Cov.: 32 AF XY: 0.186 AC XY: 13838 AN XY: 74396

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.153

Alfa AF: 0.130 Hom.: 940

Bravo AF: 0.164

Asia WGS AF: 0.264 AC: 916 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.45

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

Other links and lift over

dbSNP: rs2234489; hg19: chr20-57013873;