20-58419347-T-G

Position:

• chr20-58419347-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004738.5(VAPB):​c.211+984T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,942 control chromosomes in the GnomAD database, including 6,150 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6150 hom., cov: 32)
• Consequence: VAPB NM_004738.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAPB	NM_004738.5	c.211+984T>G		intron_variant		ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.211+984T>G		intron_variant			NP_001182606.1
VAPB	NR_036633.2	n.442+984T>G		intron_variant
VAPB	XR_001754433.3	n.442+984T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243.6	c.211+984T>G		intron_variant		1	NM_004738.5	ENSP00000417175.1
VAPB	ENST00000395802.7	c.211+984T>G		intron_variant		1		ENSP00000379147.3
VAPB	ENST00000265619.6	n.509+984T>G		intron_variant		2
VAPB	ENST00000520497.1	n.211+984T>G		intron_variant		2		ENSP00000430426.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42338 AN: 151824 Hom.: 6147 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.257

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42356 AN: 151942 Hom.: 6150 Cov.: 32 AF XY: 0.282 AC XY: 20960 AN XY: 74270

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.260

Alfa AF: 0.140 Hom.: 238

Bravo AF: 0.267

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.49

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: rs6026256; hg19: chr20-56994403;