NM_024420.3:c.-70+1443G>A

Variant names:

• chr1-186830478-G-A
• rs10798059
• NM_024420.3:c.-70+1443G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024420.3(PLA2G4A):​c.-70+1443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,100 control chromosomes in the GnomAD database, including 12,719 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 0.41 (12719 hom., cov: 29)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.-70+1443G>A		intron_variant	Intron 1 of 17	ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2	c.-70+1443G>A		intron_variant	Intron 1 of 15		NP_001298122.2
PLA2G4A	XM_011509642.3	c.-70+1428G>A		intron_variant	Intron 1 of 17		XP_011507944.1
PLA2G4A	XM_047422599.1	c.-70+1443G>A		intron_variant	Intron 1 of 14		XP_047278555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.-70+1443G>A		intron_variant	Intron 1 of 17	1	NM_024420.3	ENSP00000356436.3

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61267 AN: 150986 Hom.: 12708 Cov.: 29

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.406 AC: 61305 AN: 151100 Hom.: 12719 Cov.: 29 AF XY: 0.411 AC XY: 30342 AN XY: 73778

African (AFR) AF: 0.387 AC: 15902 AN: 41098

American (AMR) AF: 0.467 AC: 7101 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1496 AN: 3466

East Asian (EAS) AF: 0.619 AC: 3146 AN: 5084

South Asian (SAS) AF: 0.358 AC: 1712 AN: 4776

European-Finnish (FIN) AF: 0.422 AC: 4398 AN: 10428

Middle Eastern (MID) AF: 0.410 AC: 119 AN: 290

European-Non Finnish (NFE) AF: 0.388 AC: 26294 AN: 67762

Other (OTH) AF: 0.396 AC: 828 AN: 2090

Alfa AF: 0.386 Hom.: 1424

Bravo AF: 0.413

Asia WGS AF: 0.458 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.80
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10798059; hg19: chr1-186799610;