rs12749354

Variant names:

• chr1-186887116-T-C
• rs12749354
• NM_024420.3:c.116-5895T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-186887116-T-C
• chr1-186887116-T-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.116-5895T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,124 control chromosomes in the GnomAD database, including 2,413 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 0.17 (2413 hom., cov: 32)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.116-5895T>C		intron_variant	Intron 3 of 17	ENST00000367466.4	NP_077734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.116-5895T>C		intron_variant	Intron 3 of 17	1	NM_024420.3	ENSP00000356436.3
PLA2G4A	ENST00000466600.1	n.185-5895T>C		intron_variant	Intron 2 of 6	3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26446 AN: 152008 Hom.: 2410 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.174 AC: 26474 AN: 152124 Hom.: 2413 Cov.: 32 AF XY: 0.173 AC XY: 12853 AN XY: 74378

African (AFR) AF: 0.195 AC: 8110 AN: 41500

American (AMR) AF: 0.203 AC: 3092 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.136 AC: 707 AN: 5182

South Asian (SAS) AF: 0.236 AC: 1137 AN: 4820

European-Finnish (FIN) AF: 0.121 AC: 1287 AN: 10598

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10711 AN: 67990

Other (OTH) AF: 0.200 AC: 422 AN: 2112

Alfa AF: 0.167 Hom.: 1196

Bravo AF: 0.182

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.52
PhyloP100		-0.16
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: rs12749354; hg19: chr1-186856248;