rs29162

Variant names:

• chr18-9931500-C-T
• rs29162
• NM_194434.3:c.80-310C>T

Variant summary

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

The NM_194434.3(VAPA):​c.80-310C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,908 control chromosomes in the GnomAD database, including 5,339 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 0.25 (5339 hom., cov: 32)
• Consequence: VAPA NM_194434.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAPA	NM_194434.3	c.80-310C>T		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.80-310C>T		intron_variant	Intron 1 of 5	1	NM_194434.3	ENSP00000382880.3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38137 AN: 151788 Hom.: 5337 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.251 AC: 38139 AN: 151908 Hom.: 5339 Cov.: 32 AF XY: 0.246 AC XY: 18266 AN XY: 74230

African (AFR) AF: 0.168 AC: 6977 AN: 41416

American (AMR) AF: 0.241 AC: 3683 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3468

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5186

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4822

European-Finnish (FIN) AF: 0.267 AC: 2806 AN: 10492

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21237 AN: 67940

Other (OTH) AF: 0.272 AC: 576 AN: 2116

Alfa AF: 0.296 Hom.: 4930

Bravo AF: 0.246

Asia WGS AF: 0.107 AC: 374 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.70
PhyloP100		0.15
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: rs29162; hg19: chr18-9931497;