1-186870519-A-AAG

Position:

• chr1-186870519-A-AAG

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.115+4_115+5dup		splice_donor_region_variant, intron_variant		ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2	c.115+4_115+5dup		splice_donor_region_variant, intron_variant			NP_001298122.2
PLA2G4A	XM_011509642.3	c.115+4_115+5dup		splice_donor_region_variant, intron_variant			XP_011507944.1
PLA2G4A	XM_047422599.1	c.115+4_115+5dup		splice_donor_region_variant, intron_variant			XP_047278555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.115+4_115+5dup		splice_donor_region_variant, intron_variant		1	NM_024420.3	ENSP00000356436	P1
PLA2G4A	ENST00000466600.1	n.184+4_184+5dup		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 77 AN: 148470 Hom.: 0 Cov.: 32 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: 68 AN: 1442954 Hom.: 0 Cov.: 27 AF XY: 0.0000543 AC XY: 39 AN XY: 718888

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: 77 AN: 148570 Hom.: 0 Cov.: 32 AF XY: 0.000482 AC XY: 35 AN XY: 72646

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.: 0

EpiCase AF: 0.00

EpiControl AF: 0.000238

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs757481718; hg19: chr1-186839651;