rs2285714

Positions:

• chr4-109717654-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000243501.10(PLA2G12A):​c.345G>A​(p.Glu115=) variant causes a synonymous change. The variant allele was found at a frequency of 0.402 in 1,613,256 control chromosomes in the GnomAD database, including 136,736 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 0.31 (9095 hom., cov: 32)
  • Exomes 𝑓: 0.41 (127641 hom.)
• Consequence: PLA2G12A ENST00000243501.10 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12

Genes affected

PLA2G12A (HGNC:18554): (phospholipase A2 group XIIA) Secreted phospholipase A2 (sPLA2) enzymes liberate arachidonic acid from phospholipids for production of eicosanoids and exert a variety of physiologic and pathologic effects. Group XII sPLA2s, such as PLA2G12A, have relatively low specific activity and are structurally and functionally distinct from other sPLA2s (Gelb et al., 2000 [PubMed 11031251]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G12A	NM_030821.5	c.345G>A	p.Glu115=	synonymous_variant	3/4	ENST00000243501.10	NP_110448.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G12A	ENST00000243501.10	c.345G>A	p.Glu115=	synonymous_variant	3/4	1	NM_030821.5	ENSP00000243501	P3
PLA2G12A	ENST00000502283.1	c.339G>A	p.Glu113=	synonymous_variant	3/4	1		ENSP00000425274	A1
PLA2G12A	ENST00000502772.1	n.139G>A		non_coding_transcript_exon_variant	2/2	5
PLA2G12A	ENST00000507961.1	c.*55G>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	2		ENSP00000424021

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47374 AN: 151968 Hom.: 9095 Cov.: 32

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.316

GnomAD3 exomes AF: 0.374 AC: 94001 AN: 251360 Hom.: 18909 AF XY: 0.380 AC XY: 51580 AN XY: 135858

Gnomad AFR exome AF: 0.0660

Gnomad AMR exome AF: 0.389

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.228

Gnomad SAS exome AF: 0.406

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.429

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.412 AC: 601509 AN: 1461168 Hom.: 127641 Cov.: 41 AF XY: 0.411 AC XY: 298976 AN XY: 726910

Gnomad4 AFR exome AF: 0.0628

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.312 AC: 47377 AN: 152088 Hom.: 9095 Cov.: 32 AF XY: 0.310 AC XY: 23062 AN XY: 74326

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.312

Alfa AF: 0.399 Hom.: 26832

Bravo AF: 0.296

Asia WGS AF: 0.297 AC: 1034 AN: 3478

EpiCase AF: 0.415

EpiControl AF: 0.410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	9.7
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2285714; hg19: chr4-110638810; COSMIC: COSV54669383;