rs2076075

Positions:

• chr1-186854152-G-A

Variant summary

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

The NM_024420.3(PLA2G4A):​c.-69-134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 519,930 control chromosomes in the GnomAD database, including 7,602 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 0.13 (1828 hom., cov: 32)
  • Exomes 𝑓: 0.15 (5774 hom.)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.-69-134G>A		intron_variant		ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2	c.-69-134G>A		intron_variant			NP_001298122.2
PLA2G4A	XM_011509642.3	c.-69-134G>A		intron_variant			XP_011507944.1
PLA2G4A	XM_047422599.1	c.-69-134G>A		intron_variant			XP_047278555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.-69-134G>A		intron_variant		1	NM_024420.3	ENSP00000356436	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19641 AN: 151636 Hom.: 1833 Cov.: 32

Gnomad AFR AF: 0.0814

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.147 AC: 54097 AN: 368176 Hom.: 5774 AF XY: 0.144 AC XY: 27884 AN XY: 193446

Gnomad4 AFR exome AF: 0.0721

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.0734

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.129 AC: 19636 AN: 151754 Hom.: 1828 Cov.: 32 AF XY: 0.133 AC XY: 9867 AN XY: 74170

Gnomad4 AFR AF: 0.0813

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.0704

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.127

Alfa AF: 0.117 Hom.: 1710

Bravo AF: 0.143

Asia WGS AF: 0.270 AC: 936 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.077
DANN	Benign	0.62

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: rs2076075; hg19: chr1-186823284;