rs12726519

Variant names:

• chr1-186928933-C-T
• rs12726519
• NM_024420.3:c.559-3830C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.92).
• 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 rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.559-3830C>T		intron_variant	Intron 7 of 17	ENST00000367466.4	NP_077734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.559-3830C>T		intron_variant	Intron 7 of 17	1	NM_024420.3	ENSP00000356436.3
PLA2G4A	ENST00000466600.1	n.628-10075C>T		intron_variant	Intron 6 of 6	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

African (AFR) AF: 0.583 AC: 24172 AN: 41446

American (AMR) AF: 0.219 AC: 3341 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 868 AN: 3464

East Asian (EAS) AF: 0.369 AC: 1906 AN: 5164

South Asian (SAS) AF: 0.279 AC: 1346 AN: 4822

European-Finnish (FIN) AF: 0.152 AC: 1607 AN: 10578

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12328 AN: 67986

Other (OTH) AF: 0.304 AC: 642 AN: 2110

Alfa AF: 0.220 Hom.: 19231

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
PhyloP100		0.34
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: rs12726519; hg19: chr1-186898065;