rs29193

Variant names:

• chr18-9924620-G-A
• rs29193
• NM_194434.3:c.80-7190G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194434.3(VAPA):​c.80-7190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,018 control chromosomes in the GnomAD database, including 21,498 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 0.52 (21498 hom., cov: 32)
• Consequence: VAPA NM_194434.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 3 publications found

Genes affected

VAPA (HGNC:12648): (VAMP associated protein A) The protein encoded by this gene is a type IV membrane protein. It is present in the plasma membrane and intracellular vesicles. It may also be associated with the cytoskeleton. This protein may function in vesicle trafficking, membrane fusion, protein complex assembly and cell motility. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAPA	NM_194434.3	c.80-7190G>A		intron_variant	Intron 1 of 5	ENST00000400000.7	NP_919415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAPA	ENST00000400000.7	c.80-7190G>A		intron_variant	Intron 1 of 5	1	NM_194434.3	ENSP00000382880.3

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79628 AN: 151900 Hom.: 21477 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.524 AC: 79700 AN: 152018 Hom.: 21498 Cov.: 32 AF XY: 0.519 AC XY: 38591 AN XY: 74302

African (AFR) AF: 0.612 AC: 25371 AN: 41440

American (AMR) AF: 0.466 AC: 7119 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1960 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1039 AN: 5174

South Asian (SAS) AF: 0.523 AC: 2527 AN: 4828

European-Finnish (FIN) AF: 0.460 AC: 4862 AN: 10562

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34882 AN: 67958

Other (OTH) AF: 0.542 AC: 1146 AN: 2114

Alfa AF: 0.517 Hom.: 5560

Bravo AF: 0.527

Asia WGS AF: 0.389 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.36
DANN	Benign	0.66
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs29193; hg19: chr18-9924617;