NM_024420.3:c.33+6901C>T

Variant names:

• chr1-186861288-C-T
• rs12720497
• NM_024420.3:c.33+6901C>T

Variant summary

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

The NM_024420.3(PLA2G4A):​c.33+6901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,998 control chromosomes in the GnomAD database, including 5,638 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 (5638 hom., cov: 31)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.33+6901C>T		intron_variant	Intron 2 of 17	ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2	c.33+6901C>T		intron_variant	Intron 2 of 15		NP_001298122.2
PLA2G4A	XM_011509642.3	c.33+6901C>T		intron_variant	Intron 2 of 17		XP_011507944.1
PLA2G4A	XM_047422599.1	c.33+6901C>T		intron_variant	Intron 2 of 14		XP_047278555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.33+6901C>T		intron_variant	Intron 2 of 17	1	NM_024420.3	ENSP00000356436.3
PLA2G4A	ENST00000466600.1	n.102+6901C>T		intron_variant	Intron 1 of 6	3

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38005 AN: 151880 Hom.: 5641 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.0887

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.250 AC: 37999 AN: 151998 Hom.: 5638 Cov.: 31 AF XY: 0.250 AC XY: 18567 AN XY: 74268

African (AFR) AF: 0.111 AC: 4622 AN: 41496

American (AMR) AF: 0.206 AC: 3148 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3468

East Asian (EAS) AF: 0.0890 AC: 459 AN: 5160

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4812

European-Finnish (FIN) AF: 0.365 AC: 3851 AN: 10560

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22672 AN: 67932

Other (OTH) AF: 0.225 AC: 474 AN: 2110

Alfa AF: 0.244 Hom.: 1180

Bravo AF: 0.228

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		-0.37
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: rs12720497; hg19: chr1-186830420;