rs7545121

Variant names:

• chr1-186982297-A-G
• rs7545121
• NM_024420.3:c.2118+2825A>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.2118+2825A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,162 control chromosomes in the GnomAD database, including 14,174 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 0.39 (14174 hom., cov: 33)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 12 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), Ambry Genetics, Orphanet, ClinGen
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4A	NM_024420.3	MANE Select	c.2118+2825A>G		intron	N/A	NP_077734.2	P47712
	PLA2G4A	NM_001311193.2		c.1938+2825A>G		intron	N/A	NP_001298122.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4A	ENST00000367466.4	TSL:1 MANE Select	c.2118+2825A>G		intron	N/A	ENSP00000356436.3	P47712
	PLA2G4A	ENST00000851114.1		c.2118+2825A>G		intron	N/A	ENSP00000521173.1
	PLA2G4A	ENST00000851115.1		c.2118+2825A>G		intron	N/A	ENSP00000521174.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60060 AN: 152040 Hom.: 14157 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.395 AC: 60094 AN: 152162 Hom.: 14174 Cov.: 33 AF XY: 0.399 AC XY: 29692 AN XY: 74380

African (AFR) AF: 0.121 AC: 5032 AN: 41548

American (AMR) AF: 0.387 AC: 5923 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1828 AN: 3470

East Asian (EAS) AF: 0.584 AC: 3010 AN: 5158

South Asian (SAS) AF: 0.443 AC: 2134 AN: 4818

European-Finnish (FIN) AF: 0.555 AC: 5867 AN: 10580

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34856 AN: 67976

Other (OTH) AF: 0.403 AC: 852 AN: 2112

Alfa AF: 0.473 Hom.: 30911

Bravo AF: 0.368

Asia WGS AF: 0.468 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.081
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: rs7545121; hg19: chr1-186951429; COSMIC: COSV66552755;