1-186880054-A-G

Variant names:

• chr1-186880054-A-G
• rs12746200
• NM_024420.3:c.115+9538A>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.115+9538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 152,010 control chromosomes in the GnomAD database, including 577 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 0.075 (577 hom., cov: 32)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430
• Publications: 17 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 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.115+9538A>G		intron	N/A	NP_077734.2	P47712
	PLA2G4A	NM_001311193.2		c.115+9538A>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.115+9538A>G		intron	N/A	ENSP00000356436.3	P47712
	PLA2G4A	ENST00000851114.1		c.115+9538A>G		intron	N/A	ENSP00000521173.1
	PLA2G4A	ENST00000851115.1		c.115+9538A>G		intron	N/A	ENSP00000521174.1

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11343 AN: 151892 Hom.: 576 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0655

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0747 AC: 11349 AN: 152010 Hom.: 577 Cov.: 32 AF XY: 0.0738 AC XY: 5485 AN XY: 74300

African (AFR) AF: 0.0175 AC: 727 AN: 41526

American (AMR) AF: 0.126 AC: 1912 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3466

East Asian (EAS) AF: 0.0645 AC: 333 AN: 5164

South Asian (SAS) AF: 0.0654 AC: 315 AN: 4820

European-Finnish (FIN) AF: 0.0737 AC: 781 AN: 10596

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0945 AC: 6419 AN: 67926

Other (OTH) AF: 0.111 AC: 235 AN: 2108

Alfa AF: 0.0855 Hom.: 1597

Bravo AF: 0.0762

Asia WGS AF: 0.0620 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.82
PhyloP100		0.43
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: rs12746200; hg19: chr1-186849186;