rs7519192

Positions:

• chr1-186893287-A-G

Variant summary

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

The NM_024420.3(PLA2G4A):​c.264+128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 804,848 control chromosomes in the GnomAD database, including 34,524 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 0.26 (5503 hom., cov: 32)
  • Exomes 𝑓: 0.28 (29021 hom.)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.264+128A>G		intron_variant		ENST00000367466.4	NP_077734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.264+128A>G		intron_variant		1	NM_024420.3	ENSP00000356436	P1
PLA2G4A	ENST00000466600.1	n.333+128A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39043 AN: 151906 Hom.: 5494 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.283 AC: 185055 AN: 652824 Hom.: 29021 AF XY: 0.284 AC XY: 100786 AN XY: 354270

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.541

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.257 AC: 39080 AN: 152024 Hom.: 5503 Cov.: 32 AF XY: 0.259 AC XY: 19265 AN XY: 74300

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.274

Alfa AF: 0.271 Hom.: 2703

Bravo AF: 0.266

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.47

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: rs7519192; hg19: chr1-186862419; COSMIC: COSV66553580;