18-9918028-C-G

Variant names:

• chr18-9918028-C-G
• rs494015
• NM_194434.3:c.79+3693C>G

Variant summary

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

The NM_194434.3(VAPA):​c.79+3693C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,674 control chromosomes in the GnomAD database, including 9,443 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 0.34 (9443 hom., cov: 31)
• Consequence: VAPA NM_194434.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAPA	NM_194434.3	c.79+3693C>G		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.79+3693C>G		intron_variant	Intron 1 of 5	1	NM_194434.3	ENSP00000382880.3

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52217 AN: 151556 Hom.: 9439 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.344 AC: 52243 AN: 151674 Hom.: 9443 Cov.: 31 AF XY: 0.341 AC XY: 25303 AN XY: 74122

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.373

Alfa AF: 0.353 Hom.: 1211

Bravo AF: 0.338

Asia WGS AF: 0.224 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.35

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: rs494015; hg19: chr18-9918025;