rs2285714

Variant names:

• chr4-109717654-C-T
• rs2285714
• NM_030821.5:c.345G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_030821.5(PLA2G12A):​c.345G>A​(p.Glu115Glu) 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 NM_030821.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12
• Publications: 66 publications found

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]

ENSG00000285330 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLA2G12A	NM_030821.5	c.345G>A	p.Glu115Glu	synonymous_variant	Exon 3 of 4	ENST00000243501.10	NP_110448.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G12A	ENST00000243501.10	c.345G>A	p.Glu115Glu	synonymous_variant	Exon 3 of 4	1	NM_030821.5	ENSP00000243501.5
ENSG00000285330	ENST00000645635.1	c.1671G>A	p.Glu557Glu	synonymous_variant	Exon 14 of 15			ENSP00000493607.1

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

GnomAD2 exomes AF: 0.374 AC: 94001 AN: 251360 AF XY: 0.380

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 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

African (AFR) AF: 0.0628 AC: 2102 AN: 33470

American (AMR) AF: 0.381 AC: 17047 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 8812 AN: 26118

East Asian (EAS) AF: 0.228 AC: 9056 AN: 39682

South Asian (SAS) AF: 0.398 AC: 34347 AN: 86210

European-Finnish (FIN) AF: 0.394 AC: 21026 AN: 53414

Middle Eastern (MID) AF: 0.293 AC: 1688 AN: 5766

European-Non Finnish (NFE) AF: 0.436 AC: 484680 AN: 1111428

Other (OTH) AF: 0.377 AC: 22751 AN: 60364

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

African (AFR) AF: 0.0793 AC: 3295 AN: 41530

American (AMR) AF: 0.356 AC: 5432 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1112 AN: 5166

South Asian (SAS) AF: 0.385 AC: 1855 AN: 4822

European-Finnish (FIN) AF: 0.385 AC: 4065 AN: 10552

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29268 AN: 67964

Other (OTH) AF: 0.312 AC: 659 AN: 2112

Alfa AF: 0.376 Hom.: 33882

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
PhyloP100		4.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2285714; hg19: chr4-110638810; COSMIC: COSV54669383;