1-186861432-C-T

Variant names:

• chr1-186861432-C-T
• rs10911933
• NM_024420.3:c.33+7045C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024420.3(PLA2G4A):​c.33+7045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,220 control chromosomes in the GnomAD database, including 56,904 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 0.86 (56904 hom., cov: 32)
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4A	NM_024420.3	c.33+7045C>T		intron_variant	Intron 2 of 17	ENST00000367466.4	NP_077734.2
PLA2G4A	NM_001311193.2	c.33+7045C>T		intron_variant	Intron 2 of 15		NP_001298122.2
PLA2G4A	XM_011509642.3	c.33+7045C>T		intron_variant	Intron 2 of 17		XP_011507944.1
PLA2G4A	XM_047422599.1	c.33+7045C>T		intron_variant	Intron 2 of 14		XP_047278555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.33+7045C>T		intron_variant	Intron 2 of 17	1	NM_024420.3	ENSP00000356436.3
PLA2G4A	ENST00000466600.1	n.102+7045C>T		intron_variant	Intron 1 of 6	3

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131064 AN: 152102 Hom.: 56840 Cov.: 32

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.862 AC: 131188 AN: 152220 Hom.: 56904 Cov.: 32 AF XY: 0.860 AC XY: 63994 AN XY: 74428

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.859

Alfa AF: 0.833 Hom.: 26340

Bravo AF: 0.871

Asia WGS AF: 0.827 AC: 2871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.63
DANN	Benign	0.24

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: rs10911933; hg19: chr1-186830564;