rs4651330

Positions:

• chr1-186847518-C-A
• chr1-186847518-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.-69-6768C>A		intron_variant		ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2	c.-69-6768C>A		intron_variant			NP_001298122.2
PLA2G4A	XM_011509642.3	c.-69-6768C>A		intron_variant			XP_011507944.1
PLA2G4A	XM_047422599.1	c.-69-6768C>A		intron_variant			XP_047278555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.-69-6768C>A		intron_variant		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

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.788

Alfa AF: 0.772 Hom.: 9039

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4651330; hg19: chr1-186816650;