chr18-9929674-A-G

Variant names:

• chr18-9929674-A-G
• rs29202
• NM_194434.3:c.80-2136A>G

Variant summary

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

The NM_194434.3(VAPA):​c.80-2136A>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
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194434.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAPA	NM_194434.3	MANE Select	c.80-2136A>G		intron	N/A	NP_919415.2
	VAPA	NM_003574.6		c.80-2136A>G		intron	N/A	NP_003565.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAPA	ENST00000400000.7	TSL:1 MANE Select	c.80-2136A>G		intron	N/A	ENSP00000382880.3
	VAPA	ENST00000340541.4	TSL:5	c.80-2136A>G		intron	N/A	ENSP00000345656.4
	VAPA	ENST00000577901.5	TSL:2	n.285-2136A>G		intron	N/A

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

African (AFR) AF: 0.103 AC: 4292 AN: 41492

American (AMR) AF: 0.0919 AC: 1404 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3470

East Asian (EAS) AF: 0.0672 AC: 348 AN: 5182

South Asian (SAS) AF: 0.0618 AC: 298 AN: 4820

European-Finnish (FIN) AF: 0.115 AC: 1214 AN: 10590

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0553 AC: 3762 AN: 68000

Other (OTH) AF: 0.0634 AC: 134 AN: 2114

Alfa AF: 0.0648 Hom.: 73

Bravo AF: 0.0772

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		-0.33
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: rs29202; hg19: chr18-9929671;