15-42142639-T-C

Variant names:

• chr15-42142639-T-C
• rs1356410
• NM_213600.4:c.2218A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_213600.4(PLA2G4F):​c.2218A>G​(p.Met740Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 1,613,624 control chromosomes in the GnomAD database, including 402,641 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. M740K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.74 (42634 hom., cov: 30)
  • Exomes 𝑓: 0.70 (360007 hom.)
• Consequence: PLA2G4F NM_213600.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 35 publications found

Genes affected

PLA2G4F (HGNC:27396): (phospholipase A2 group IVF) Predicted to enable calcium ion binding activity; calcium-dependent phospholipase A2 activity; and calcium-dependent phospholipid binding activity. Predicted to be involved in glycerophospholipid catabolic process. Predicted to act upstream of or within several processes, including arachidonic acid secretion; cellular response to antibiotic; and prostaglandin biosynthetic process. Predicted to be located in cytoplasm. Predicted to be active in cytosol; ruffle membrane; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.35062E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4F	NM_213600.4	c.2218A>G	p.Met740Val	missense_variant	Exon 19 of 20	ENST00000397272.7	NP_998765.3
PLA2G4F	NR_033151.2	n.2232A>G		non_coding_transcript_exon_variant	Exon 18 of 19
PLA2G4F	XR_931785.1	n.2421A>G		non_coding_transcript_exon_variant	Exon 20 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4F	ENST00000397272.7	c.2218A>G	p.Met740Val	missense_variant	Exon 19 of 20	1	NM_213600.4	ENSP00000380442.4

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112901 AN: 151820 Hom.: 42590 Cov.: 30

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.706

GnomAD2 exomes AF: 0.744 AC: 187056 AN: 251312 AF XY: 0.740

Gnomad AFR exome AF: 0.853

Gnomad AMR exome AF: 0.805

Gnomad ASJ exome AF: 0.598

Gnomad EAS exome AF: 0.878

Gnomad FIN exome AF: 0.790

Gnomad NFE exome AF: 0.672

Gnomad OTH exome AF: 0.707

GnomAD4 exome AF: 0.699 AC: 1021204 AN: 1461686 Hom.: 360007 Cov.: 63 AF XY: 0.701 AC XY: 509725 AN XY: 727148

African (AFR) AF: 0.850 AC: 28464 AN: 33476

American (AMR) AF: 0.798 AC: 35673 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 15521 AN: 26130

East Asian (EAS) AF: 0.884 AC: 35099 AN: 39700

South Asian (SAS) AF: 0.828 AC: 71406 AN: 86246

European-Finnish (FIN) AF: 0.783 AC: 41799 AN: 53408

Middle Eastern (MID) AF: 0.672 AC: 3877 AN: 5768

European-Non Finnish (NFE) AF: 0.672 AC: 746686 AN: 1111858

Other (OTH) AF: 0.707 AC: 42679 AN: 60384

GnomAD4 genome AF: 0.744 AC: 113006 AN: 151938 Hom.: 42634 Cov.: 30 AF XY: 0.750 AC XY: 55660 AN XY: 74250

African (AFR) AF: 0.844 AC: 34987 AN: 41432

American (AMR) AF: 0.737 AC: 11251 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2102 AN: 3466

East Asian (EAS) AF: 0.875 AC: 4513 AN: 5156

South Asian (SAS) AF: 0.834 AC: 4013 AN: 4812

European-Finnish (FIN) AF: 0.788 AC: 8321 AN: 10556

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.671 AC: 45561 AN: 67930

Other (OTH) AF: 0.708 AC: 1494 AN: 2110

Alfa AF: 0.690 Hom.: 178756

Bravo AF: 0.742

TwinsUK AF: 0.668 AC: 2478

ALSPAC AF: 0.680 AC: 2622

ESP6500AA AF: 0.843 AC: 3714

ESP6500EA AF: 0.665 AC: 5720

ExAC AF: 0.746 AC: 90509

Asia WGS AF: 0.863 AC: 3002 AN: 3478

EpiCase AF: 0.662

EpiControl AF: 0.655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0080
DANN	Benign	0.55
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	7.4e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-1.4
PrimateAI	Benign	0.23	T
REVEL	Benign	0.021
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.032
ClinPred		0.048	T
GERP RS		-9.4
Varity_R		0.080
gMVP		0.34
Mutation Taster		=99/1	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: rs1356410; hg19: chr15-42434837; COSMIC: COSV107330047; COSMIC: COSV107330047;