1-186870529-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_024420.3(PLA2G4A):c.115+13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLA2G4A NM_024420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-186870529-T-A is Benign according to our data. Variant chr1-186870529-T-A is described in ClinVar as [Benign]. Clinvar id is 1895556.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-186870529-T-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G4A	NM_024420.3	c.115+13T>A		intron_variant		ENST00000367466.4
PLA2G4A	NM_001311193.2	c.115+13T>A		intron_variant
PLA2G4A	XM_011509642.3	c.115+13T>A		intron_variant
PLA2G4A	XM_047422599.1	c.115+13T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.115+13T>A		intron_variant		1	NM_024420.3	P1
PLA2G4A	ENST00000466600.1	n.184+13T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 474 AN: 141612 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00428

Gnomad AMI AF: 0.00115

Gnomad AMR AF: 0.00173

Gnomad ASJ AF: 0.000598

Gnomad EAS AF: 0.00756

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00204

GnomAD3 exomes AF: 0.00148 AC: 356 AN: 240500 Hom.: 2 AF XY: 0.00146 AC XY: 190 AN XY: 129992

Gnomad AFR exome AF: 0.000516

Gnomad AMR exome AF: 0.000303

Gnomad ASJ exome AF: 0.000306

Gnomad EAS exome AF: 0.00232

Gnomad SAS exome AF: 0.000827

Gnomad FIN exome AF: 0.00709

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.00202

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000784 AC: 1083 AN: 1381418 Hom.: 3 Cov.: 25 AF XY: 0.000735 AC XY: 508 AN XY: 691088

Gnomad4 AFR exome AF: 0.000569

Gnomad4 AMR exome AF: 0.000477

Gnomad4 ASJ exome AF: 0.000275

Gnomad4 EAS exome AF: 0.000911

Gnomad4 SAS exome AF: 0.000439

Gnomad4 FIN exome AF: 0.00603

Gnomad4 NFE exome AF: 0.000558

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00336 AC: 476 AN: 141706 Hom.: 0 Cov.: 32 AF XY: 0.00346 AC XY: 240 AN XY: 69442

Gnomad4 AFR AF: 0.00433

Gnomad4 AMR AF: 0.00173

Gnomad4 ASJ AF: 0.000598

Gnomad4 EAS AF: 0.00737

Gnomad4 SAS AF: 0.00460

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00147

Gnomad4 OTH AF: 0.00202

Alfa AF: 0.0112 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.20
Dann	Benign	0.61

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: rs67340624; hg19: chr1-186839661;