rs2268924

Positions:

• chr20-58403122-A-G
• chr20-58403122-A-T

Variant summary

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

The ENST00000475243.6(VAPB):​c.58+13605A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,040 control chromosomes in the GnomAD database, including 8,860 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 0.33 (8860 hom., cov: 32)
• Consequence: VAPB ENST00000475243.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAPB	NM_004738.5	c.58+13605A>G		intron_variant		ENST00000475243.6	NP_004729.1
VAPB	NM_001195677.2	c.58+13605A>G		intron_variant			NP_001182606.1
VAPB	NR_036633.2	n.289+13605A>G		intron_variant, non_coding_transcript_variant
VAPB	XR_001754433.3	n.289+13605A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPB	ENST00000475243.6	c.58+13605A>G		intron_variant		1	NM_004738.5	ENSP00000417175	P1
VAPB	ENST00000395802.7	c.58+13605A>G		intron_variant		1		ENSP00000379147
VAPB	ENST00000520497.1	c.58+13605A>G		intron_variant, NMD_transcript_variant		2		ENSP00000430426
VAPB	ENST00000265619.6	n.356+12782A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50912 AN: 151922 Hom.: 8857 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.335 AC: 50932 AN: 152040 Hom.: 8860 Cov.: 32 AF XY: 0.341 AC XY: 25316 AN XY: 74312

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.295

Alfa AF: 0.347 Hom.: 1429

Bravo AF: 0.311

Asia WGS AF: 0.329 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.63

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: rs2268924; hg19: chr20-56978178;