1-186893380-G-A

Variant names:

• chr1-186893380-G-A
• rs7542180
• NM_024420.3:c.264+221G>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.264+221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,974 control chromosomes in the GnomAD database, including 12,338 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 0.37 (12338 hom., cov: 31)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.264+221G>A		intron_variant	Intron 4 of 17	ENST00000367466.4	NP_077734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.264+221G>A		intron_variant	Intron 4 of 17	1	NM_024420.3	ENSP00000356436.3
PLA2G4A	ENST00000466600.1	n.333+221G>A		intron_variant	Intron 3 of 6	3

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56487 AN: 151856 Hom.: 12332 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.372 AC: 56513 AN: 151974 Hom.: 12338 Cov.: 31 AF XY: 0.372 AC XY: 27659 AN XY: 74274

African (AFR) AF: 0.137 AC: 5673 AN: 41468

American (AMR) AF: 0.330 AC: 5043 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1685 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2403 AN: 5172

South Asian (SAS) AF: 0.357 AC: 1720 AN: 4822

European-Finnish (FIN) AF: 0.524 AC: 5512 AN: 10516

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33110 AN: 67946

Other (OTH) AF: 0.380 AC: 801 AN: 2108

Alfa AF: 0.298 Hom.: 884

Bravo AF: 0.346

Asia WGS AF: 0.409 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.45
DANN	Benign	0.39
PhyloP100		-0.36
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: rs7542180; hg19: chr1-186862512;