1-186839211-G-T

Variant names:

• chr1-186839211-G-T
• rs3820185
• NM_024420.3:c.-70+10176G>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.-70+10176G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,052 control chromosomes in the GnomAD database, including 10,228 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 0.36 (10228 hom., cov: 32)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• 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), 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4A	NM_024420.3	MANE Select	c.-70+10176G>T		intron	N/A	NP_077734.2
	PLA2G4A	NM_001311193.2		c.-70+10176G>T		intron	N/A	NP_001298122.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4A	ENST00000367466.4	TSL:1 MANE Select	c.-70+10176G>T		intron	N/A	ENSP00000356436.3

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55050 AN: 151934 Hom.: 10227 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.362 AC: 55078 AN: 152052 Hom.: 10228 Cov.: 32 AF XY: 0.368 AC XY: 27332 AN XY: 74324

African (AFR) AF: 0.370 AC: 15363 AN: 41468

American (AMR) AF: 0.401 AC: 6131 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1399 AN: 3470

East Asian (EAS) AF: 0.578 AC: 2980 AN: 5152

South Asian (SAS) AF: 0.311 AC: 1503 AN: 4826

European-Finnish (FIN) AF: 0.379 AC: 4007 AN: 10562

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22518 AN: 67966

Other (OTH) AF: 0.360 AC: 762 AN: 2114

Alfa AF: 0.344 Hom.: 17050

Bravo AF: 0.368

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.75
DANN	Benign	0.71
PhyloP100		-0.060
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: rs3820185; hg19: chr1-186808343;