Genetic Variant VAPA:c.417+5012T>G (chr18-9942078-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_194434.3(VAPA):c.417+5012T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,126 control chromosomes in the GnomAD database, including 1,826 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 0.15 ( 1826 hom., cov: 32)

Consequence

VAPA
NM_194434.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

Variant links:

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]

VAPA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAPA	NM_194434.3 link	c.417+5012T>G		intron_variant	Intron 4 of 5	ENST00000400000.7	NP_919415.2	Q9P0L0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAPA	ENST00000400000.7 link	c.417+5012T>G		intron_variant	Intron 4 of 5	1	NM_194434.3	ENSP00000382880.3		Q9P0L0-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23081

AN:

152008

Hom.:

1814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0870

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.149

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

GnomAD4 genome

AF:

0.152

AC:

23114

AN:

152126

Hom.:

1826

Cov.:

AF XY:

0.154

AC XY:

11470

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.0870

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.129

Hom.:

2794

Bravo

AF:

0.153

Asia WGS

AF:

0.174

AC:

603

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.42

DANN

Benign

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over