Variant 1-186870519-A-AAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_024420.3(PLA2G4A):c.115+4_115+5dup variant causes a splice donor region, intron change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PLA2G4A
NM_024420.3 splice_donor_region, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48

Variant links:

Genes affected

PLA2G4A (HGNC:9035): (phospholipase A2 group IVA) This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca(2+) levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

PLA2G4A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PLA2G4A	NM_024420.3 linkuse as main transcript	c.115+4_115+5dup	splice_donor_region_variant, intron_variant	ENST00000367466.4
PLA2G4A	NM_001311193.2 linkuse as main transcript	c.115+4_115+5dup	splice_donor_region_variant, intron_variant
PLA2G4A	XM_011509642.3 linkuse as main transcript	c.115+4_115+5dup	splice_donor_region_variant, intron_variant
PLA2G4A	XM_047422599.1 linkuse as main transcript	c.115+4_115+5dup	splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G4A	ENST00000367466.4 linkuse as main transcript	c.115+4_115+5dup		splice_donor_region_variant, intron_variant		1	NM_024420.3	P1
PLA2G4A	ENST00000466600.1 linkuse as main transcript	n.184+4_184+5dup		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148470

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000348

Gnomad AMI

AF:

0.00112

Gnomad AMR

AF:

0.000470

Gnomad ASJ

AF:

0.000582

Gnomad EAS

AF:

0.000793

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.00230

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000284

Gnomad OTH

AF:

0.000978

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000471

AC:

AN:

1442954

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

718888

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.0000438

Gnomad4 OTH exome

AF:

0.0000503

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000518

AC:

AN:

148570

Hom.:

Cov.:

AF XY:

0.000482

AC XY:

AN XY:

72646

show subpopulations

Gnomad4 AFR

AF:

0.000372

Gnomad4 AMR

AF:

0.000402

Gnomad4 ASJ

AF:

0.000582

Gnomad4 EAS

AF:

0.000795

Gnomad4 SAS

AF:

0.00129

Gnomad4 FIN

AF:

0.00230

Gnomad4 NFE

AF:

0.000284

Gnomad4 OTH

AF:

0.000484

Alfa

AF:

0.00166

Hom.:

EpiCase

AF:

0.00

EpiControl

AF:

0.000238

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 07, 2022

This sequence change falls in intron 3 of the PLA2G4A gene. It does not directly change the encoded amino acid sequence of the PLA2G4A protein. It affects a nucleotide within the consensus splice site. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PLA2G4A-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over