rs4651343

Variant names:

• chr1-186948855-C-A
• rs4651343
• NM_024420.3:c.1265-1802C>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.1265-1802C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,992 control chromosomes in the GnomAD database, including 5,373 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 0.25 (5373 hom., cov: 32)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.1265-1802C>A		intron_variant	Intron 12 of 17	ENST00000367466.4	NP_077734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.1265-1802C>A		intron_variant	Intron 12 of 17	1	NM_024420.3	ENSP00000356436.3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38441 AN: 151874 Hom.: 5359 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.253 AC: 38483 AN: 151992 Hom.: 5373 Cov.: 32 AF XY: 0.256 AC XY: 18988 AN XY: 74296

African (AFR) AF: 0.179 AC: 7434 AN: 41480

American (AMR) AF: 0.400 AC: 6112 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 671 AN: 3470

East Asian (EAS) AF: 0.157 AC: 812 AN: 5158

South Asian (SAS) AF: 0.340 AC: 1635 AN: 4802

European-Finnish (FIN) AF: 0.259 AC: 2734 AN: 10554

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18226 AN: 67946

Other (OTH) AF: 0.271 AC: 573 AN: 2112

Alfa AF: 0.264 Hom.: 2995

Bravo AF: 0.262

Asia WGS AF: 0.267 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		1.1
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: rs4651343; hg19: chr1-186917987;