rs12726519

Positions:

• chr1-186928933-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.559-3830C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,050 control chromosomes in the GnomAD database, including 9,630 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 0.31 (9630 hom., cov: 32)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.559-3830C>T		intron_variant		ENST00000367466.4	NP_077734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.559-3830C>T		intron_variant		1	NM_024420.3	ENSP00000356436	P1
PLA2G4A	ENST00000466600.1	n.628-10075C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46406 AN: 151932 Hom.: 9616 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.305 AC: 46445 AN: 152050 Hom.: 9630 Cov.: 32 AF XY: 0.303 AC XY: 22519 AN XY: 74326

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.304

Alfa AF: 0.204 Hom.: 7126

Bravo AF: 0.322

Asia WGS AF: 0.308 AC: 1070 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.25

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: rs12726519; hg19: chr1-186898065;