rs3767221

Variant names:

• chr1-19975288-A-C
• rs3767221
• NM_001395463.1:c.*413T>G

Variant summary

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

The NM_001395463.1(PLA2G2A):​c.*413T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 184,764 control chromosomes in the GnomAD database, including 11,437 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 0.33 (9057 hom., cov: 32)
  • Exomes 𝑓: 0.36 (2380 hom.)
• Consequence: PLA2G2A NM_001395463.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721

Genes affected

PLA2G2A (HGNC:9031): (phospholipase A2 group IIA) The protein encoded by this gene is a member of the phospholipase A2 family (PLA2). PLA2s constitute a diverse family of enzymes with respect to sequence, function, localization, and divalent cation requirements. This gene product belongs to group II, which contains secreted form of PLA2, an extracellular enzyme that has a low molecular mass and requires calcium ions for catalysis. It catalyzes the hydrolysis of the sn-2 fatty acid acyl ester bond of phosphoglycerides, releasing free fatty acids and lysophospholipids, and thought to participate in the regulation of the phospholipid metabolism in biomembranes. Several alternatively spliced transcript variants with different 5' UTRs have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1	c.*413T>G		downstream_gene_variant		ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.*413T>G		downstream_gene_variant		1	NM_001395463.1	ENSP00000504762.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49557 AN: 151854 Hom.: 9067 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.364 AC: 11936 AN: 32792 Hom.: 2380 AF XY: 0.367 AC XY: 6259 AN XY: 17058

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.326 AC: 49551 AN: 151972 Hom.: 9057 Cov.: 32 AF XY: 0.332 AC XY: 24640 AN XY: 74264

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.313

Alfa AF: 0.342 Hom.: 1160

Bravo AF: 0.307

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3767221; hg19: chr1-20301781;