chr15-42142639-T-C

Position:

• chr15-42142639-T-C

Variant summary

Our verdict is Benign. Variant got -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. 13/18 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 same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PLA2G4F	NM_213600.4	c.2218A>G	p.Met740Val	missense_variant	19/20	ENST00000397272.7	NP_998765.3
PLA2G4F	NR_033151.2	n.2232A>G		non_coding_transcript_exon_variant	18/19
PLA2G4F	XR_931785.1	n.2421A>G		non_coding_transcript_exon_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4F	ENST00000397272.7	c.2218A>G	p.Met740Val	missense_variant	19/20	1	NM_213600.4	ENSP00000380442	P1
PLA2G4F	ENST00000290497.11	c.*1962A>G		3_prime_UTR_variant, NMD_transcript_variant	18/19	1		ENSP00000290497
PLA2G4F	ENST00000562320.1	c.*23A>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	1		ENSP00000455037
PLA2G4F	ENST00000569985.5	c.*1262A>G		3_prime_UTR_variant, NMD_transcript_variant	19/20	1		ENSP00000454330

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

GnomAD3 exomes AF: 0.744 AC: 187056 AN: 251312 Hom.: 70645 AF XY: 0.740 AC XY: 100467 AN XY: 135818

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 SAS exome AF: 0.828

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

Gnomad4 AFR exome AF: 0.850

Gnomad4 AMR exome AF: 0.798

Gnomad4 ASJ exome AF: 0.594

Gnomad4 EAS exome AF: 0.884

Gnomad4 SAS exome AF: 0.828

Gnomad4 FIN exome AF: 0.783

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.707

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

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.708

Alfa AF: 0.680 Hom.: 91700

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
MutationTaster	Benign	1.0	P;P
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

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: rs1356410; hg19: chr15-42434837;