rs7526089

chr1-186983499-C-T

Variant summary

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

The NM_024420.3(PLA2G4A):c.2118+4027C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,058 control chromosomes in the GnomAD database, including 6,596 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 0.22 (6596 hom., cov: 31)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G4A	NM_024420.3	c.2118+4027C>T		intron_variant		ENST00000367466.4
PLA2G4A	NM_001311193.2	c.1938+4027C>T		intron_variant
PLA2G4A	XM_005245267.5	c.2133+4027C>T		intron_variant
PLA2G4A	XM_011509642.3	c.2118+4027C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.2118+4027C>T		intron_variant		1	NM_024420.3	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34111 AN: 151940 Hom.: 6577 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.225 AC: 34159 AN: 152058 Hom.: 6596 Cov.: 31 AF XY: 0.220 AC XY: 16338 AN XY: 74348

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.0781

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.0864

Gnomad4 NFE AF: 0.0966

Gnomad4 OTH AF: 0.214

Alfa AF: 0.182 Hom.: 703

Bravo AF: 0.250

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.14
Dann	Benign	0.26

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: rs7526089; hg19: chr1-186952631;