1-186847518-C-A

Variant names:

• chr1-186847518-C-A
• rs4651330
• NM_024420.3:c.-69-6768C>A

Variant summary

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

The NM_024420.3(PLA2G4A):​c.-69-6768C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 151,916 control chromosomes in the GnomAD database, including 44,130 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 0.76 (44130 hom., cov: 31)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.-69-6768C>A		intron_variant	Intron 1 of 17	ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2	c.-69-6768C>A		intron_variant	Intron 1 of 15		NP_001298122.2
PLA2G4A	XM_011509642.3	c.-69-6768C>A		intron_variant	Intron 1 of 17		XP_011507944.1
PLA2G4A	XM_047422599.1	c.-69-6768C>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.-69-6768C>A		intron_variant	Intron 1 of 17	1	NM_024420.3	ENSP00000356436.3

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115014 AN: 151800 Hom.: 44105 Cov.: 31

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.758 AC: 115087 AN: 151916 Hom.: 44130 Cov.: 31 AF XY: 0.758 AC XY: 56291 AN XY: 74242

African (AFR) AF: 0.633 AC: 26209 AN: 41402

American (AMR) AF: 0.825 AC: 12554 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2880 AN: 3466

East Asian (EAS) AF: 0.782 AC: 4033 AN: 5158

South Asian (SAS) AF: 0.829 AC: 3983 AN: 4806

European-Finnish (FIN) AF: 0.768 AC: 8120 AN: 10568

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54781 AN: 67974

Other (OTH) AF: 0.788 AC: 1666 AN: 2114

Alfa AF: 0.778 Hom.: 15841

Bravo AF: 0.753

Asia WGS AF: 0.802 AC: 2786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.79
PhyloP100		-0.87
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: rs4651330; hg19: chr1-186816650;