rs29202

Positions:

• chr18-9929674-A-G

Variant summary

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

The NM_194434.3(VAPA):​c.80-2136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 152,144 control chromosomes in the GnomAD database, including 511 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 0.076 (511 hom., cov: 32)
• Consequence: VAPA NM_194434.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAPA	NM_194434.3	c.80-2136A>G		intron_variant		ENST00000400000.7	NP_919415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPA	ENST00000400000.7	c.80-2136A>G		intron_variant		1	NM_194434.3	ENSP00000382880	P1

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11621 AN: 152026 Hom.: 509 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0553

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0765 AC: 11639 AN: 152144 Hom.: 511 Cov.: 32 AF XY: 0.0791 AC XY: 5885 AN XY: 74390

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.0618

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0553

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0636 Hom.: 64

Bravo AF: 0.0772

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.77

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: rs29202; hg19: chr18-9929671;