rs2307279

Positions:

• chr19-48105341-C-G

Variant summary

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

The NM_003706.3(PLA2G4C):​c.112G>C​(p.Ala38Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 1,610,406 control chromosomes in the GnomAD database, including 14,359 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (5540 hom., cov: 30)
  • Exomes 𝑓: 0.067 (8819 hom.)
• Consequence: PLA2G4C NM_003706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

Genes affected

PLA2G4C (HGNC:9037): (phospholipase A2 group IVC) This gene encodes a protein which is a member of the phospholipase A2 enzyme family which hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids, both of which serve as precursors in the production of signaling molecules. The encoded protein has been shown to be a calcium-independent and membrane bound enzyme. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5327334E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4C	NM_003706.3	c.112G>C	p.Ala38Pro	missense_variant	3/17	ENST00000599921.6	NP_003697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4C	ENST00000599921.6	c.112G>C	p.Ala38Pro	missense_variant	3/17	1	NM_003706.3	ENSP00000469473.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28289 AN: 151926 Hom.: 5525 Cov.: 30

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0429

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.109 AC: 27273 AN: 250114 Hom.: 3436 AF XY: 0.102 AC XY: 13827 AN XY: 135252

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.0545

Gnomad ASJ exome AF: 0.0907

Gnomad EAS exome AF: 0.269

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.0754

Gnomad NFE exome AF: 0.0457

Gnomad OTH exome AF: 0.0980

GnomAD4 exome AF: 0.0675 AC: 98378 AN: 1458362 Hom.: 8819 Cov.: 30 AF XY: 0.0681 AC XY: 49404 AN XY: 725624

Gnomad4 AFR exome AF: 0.519

Gnomad4 AMR exome AF: 0.0598

Gnomad4 ASJ exome AF: 0.0883

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0712

Gnomad4 NFE exome AF: 0.0392

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.186 AC: 28342 AN: 152044 Hom.: 5540 Cov.: 30 AF XY: 0.184 AC XY: 13669 AN XY: 74344

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.0981

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0716

Gnomad4 NFE AF: 0.0429

Gnomad4 OTH AF: 0.164

Alfa AF: 0.0832 Hom.: 514

Bravo AF: 0.204

TwinsUK AF: 0.0413 AC: 153

ALSPAC AF: 0.0392 AC: 151

ESP6500AA AF: 0.483 AC: 2130

ESP6500EA AF: 0.0444 AC: 382

ExAC AF: 0.117 AC: 14188

Asia WGS AF: 0.218 AC: 759 AN: 3478

EpiCase AF: 0.0463

EpiControl AF: 0.0477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.6
DANN	Benign	0.92
DEOGEN2	Benign	0.00019	.;.;T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.50	T;T;T;T
MetaRNN	Benign	0.00015	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	.;N;N;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	.;N;.;.
REVEL	Benign	0.028
Sift	Benign	0.095	.;T;.;.
Sift4G	Uncertain	0.058	T;T;T;.
Polyphen		0.58	.;.;P;.
Vest4		0.068
MPC		0.54
ClinPred		0.0078	T
GERP RS		0.30
Varity_R		0.17
gMVP		0.38

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: rs2307279; hg19: chr19-48608598; COSMIC: COSV62784214; COSMIC: COSV62784214;