1-186978092-G-C

Variant names:

• chr1-186978092-G-C
• rs10157410
• NM_024420.3:c.1960+304G>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.1960+304G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,978 control chromosomes in the GnomAD database, including 5,000 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 0.20 (5000 hom., cov: 32)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.1960+304G>C		intron_variant	Intron 16 of 17	ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2	c.1780+304G>C		intron_variant	Intron 14 of 15		NP_001298122.2
PLA2G4A	XM_005245267.5	c.1975+304G>C		intron_variant	Intron 14 of 15		XP_005245324.2
PLA2G4A	XM_011509642.3	c.1960+304G>C		intron_variant	Intron 16 of 17		XP_011507944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.1960+304G>C		intron_variant	Intron 16 of 17	1	NM_024420.3	ENSP00000356436.3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30865 AN: 151862 Hom.: 4992 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0782

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0866

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.0967

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.203 AC: 30894 AN: 151978 Hom.: 5000 Cov.: 32 AF XY: 0.200 AC XY: 14824 AN XY: 74294

African (AFR) AF: 0.448 AC: 18571 AN: 41432

American (AMR) AF: 0.191 AC: 2921 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0782 AC: 271 AN: 3464

East Asian (EAS) AF: 0.122 AC: 631 AN: 5180

South Asian (SAS) AF: 0.100 AC: 481 AN: 4806

European-Finnish (FIN) AF: 0.0866 AC: 914 AN: 10556

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.0967 AC: 6573 AN: 67962

Other (OTH) AF: 0.199 AC: 420 AN: 2108

Alfa AF: 0.0640 Hom.: 111

Bravo AF: 0.225

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.55
PhyloP100		-0.98
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: rs10157410; hg19: chr1-186947224;