rs2307276

Positions:

• chr19-48061950-G-A

Variant summary

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

The NM_003706.3(PLA2G4C):​c.1257+48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,589,648 control chromosomes in the GnomAD database, including 1,419 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 0.055 (342 hom., cov: 31)
  • Exomes 𝑓: 0.034 (1077 hom.)
• Consequence: PLA2G4C NM_003706.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512

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]

PLA2G4C-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4C	NM_003706.3	c.1257+48C>T		intron_variant		ENST00000599921.6	NP_003697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4C	ENST00000599921.6	c.1257+48C>T		intron_variant		1	NM_003706.3	ENSP00000469473.1
PLA2G4C	ENST00000595161.5	c.321+48C>T		intron_variant		3		ENSP00000469528.1

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8398 AN: 151976 Hom.: 343 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0569

GnomAD3 exomes AF: 0.0329 AC: 7987 AN: 242532 Hom.: 245 AF XY: 0.0314 AC XY: 4129 AN XY: 131486

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.0259

Gnomad ASJ exome AF: 0.0418

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0133

Gnomad FIN exome AF: 0.0131

Gnomad NFE exome AF: 0.0352

Gnomad OTH exome AF: 0.0419

GnomAD4 exome AF: 0.0342 AC: 49167 AN: 1437554 Hom.: 1077 Cov.: 27 AF XY: 0.0334 AC XY: 23917 AN XY: 715850

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.0291

Gnomad4 ASJ exome AF: 0.0422

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.0135

Gnomad4 NFE exome AF: 0.0349

Gnomad4 OTH exome AF: 0.0393

GnomAD4 genome AF: 0.0553 AC: 8408 AN: 152094 Hom.: 342 Cov.: 31 AF XY: 0.0532 AC XY: 3957 AN XY: 74344

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0447

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0142

Gnomad4 NFE AF: 0.0352

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0470 Hom.: 51

Bravo AF: 0.0626

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.90

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: rs2307276; hg19: chr19-48565207;