rs2076075

Variant names:

• chr1-186854152-G-A
• rs2076075
• NM_024420.3:c.-69-134G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-186854152-G-A
• chr1-186854152-G-C

Variant summary

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

The NM_024420.3(PLA2G4A):​c.-69-134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 519,930 control chromosomes in the GnomAD database, including 7,602 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 0.13 (1828 hom., cov: 32)
  • Exomes 𝑓: 0.15 (5774 hom.)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.-69-134G>A		intron_variant	Intron 1 of 17	ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2	c.-69-134G>A		intron_variant	Intron 1 of 15		NP_001298122.2
PLA2G4A	XM_011509642.3	c.-69-134G>A		intron_variant	Intron 1 of 17		XP_011507944.1
PLA2G4A	XM_047422599.1	c.-69-134G>A		intron_variant	Intron 1 of 14		XP_047278555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.-69-134G>A		intron_variant	Intron 1 of 17	1	NM_024420.3	ENSP00000356436.3
PLA2G4A	ENST00000466600.1	n.-134G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19641 AN: 151636 Hom.: 1833 Cov.: 32

Gnomad AFR AF: 0.0814

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.147 AC: 54097 AN: 368176 Hom.: 5774 AF XY: 0.144 AC XY: 27884 AN XY: 193446

African (AFR) AF: 0.0721 AC: 767 AN: 10632

American (AMR) AF: 0.283 AC: 4096 AN: 14476

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 846 AN: 11528

East Asian (EAS) AF: 0.452 AC: 13114 AN: 28982

South Asian (SAS) AF: 0.102 AC: 2821 AN: 27532

European-Finnish (FIN) AF: 0.118 AC: 3216 AN: 27158

Middle Eastern (MID) AF: 0.0723 AC: 119 AN: 1646

European-Non Finnish (NFE) AF: 0.116 AC: 26057 AN: 224234

Other (OTH) AF: 0.139 AC: 3061 AN: 21988

GnomAD4 genome AF: 0.129 AC: 19636 AN: 151754 Hom.: 1828 Cov.: 32 AF XY: 0.133 AC XY: 9867 AN XY: 74170

African (AFR) AF: 0.0813 AC: 3370 AN: 41450

American (AMR) AF: 0.238 AC: 3613 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 244 AN: 3466

East Asian (EAS) AF: 0.483 AC: 2490 AN: 5156

South Asian (SAS) AF: 0.102 AC: 492 AN: 4816

European-Finnish (FIN) AF: 0.111 AC: 1175 AN: 10568

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.117 AC: 7900 AN: 67810

Other (OTH) AF: 0.127 AC: 266 AN: 2102

Alfa AF: 0.123 Hom.: 3439

Bravo AF: 0.143

Asia WGS AF: 0.270 AC: 936 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.077
DANN	Benign	0.62
PhyloP100		-1.3
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: rs2076075; hg19: chr1-186823284;