rs7519192

Variant names:

• chr1-186893287-A-G
• rs7519192
• NM_024420.3:c.264+128A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

PLA2G4A Gene-Disease associations (from GenCC):

• cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics
• cryptogenic multifocal ulcerous stenosing enteritis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4A	NM_024420.3	MANE Select	c.264+128A>G		intron	N/A	NP_077734.2
	PLA2G4A	NM_001311193.2		c.264+128A>G		intron	N/A	NP_001298122.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4A	ENST00000367466.4	TSL:1 MANE Select	c.264+128A>G		intron	N/A	ENSP00000356436.3
	PLA2G4A	ENST00000466600.1	TSL:3	n.333+128A>G		intron	N/A

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

African (AFR) AF: 0.185 AC: 3374 AN: 18202

American (AMR) AF: 0.541 AC: 23420 AN: 43296

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4016 AN: 21012

East Asian (EAS) AF: 0.159 AC: 5673 AN: 35724

South Asian (SAS) AF: 0.347 AC: 24161 AN: 69592

European-Finnish (FIN) AF: 0.259 AC: 10635 AN: 41076

Middle Eastern (MID) AF: 0.237 AC: 840 AN: 3540

European-Non Finnish (NFE) AF: 0.269 AC: 104049 AN: 386416

Other (OTH) AF: 0.262 AC: 8887 AN: 33966

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

African (AFR) AF: 0.187 AC: 7743 AN: 41472

American (AMR) AF: 0.403 AC: 6157 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3464

East Asian (EAS) AF: 0.161 AC: 833 AN: 5160

South Asian (SAS) AF: 0.339 AC: 1632 AN: 4814

European-Finnish (FIN) AF: 0.261 AC: 2753 AN: 10564

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18396 AN: 67974

Other (OTH) AF: 0.274 AC: 579 AN: 2110

Alfa AF: 0.269 Hom.: 2980

Bravo AF: 0.266

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.47
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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