rs5753472

Positions:

• chr22-31137239-G-A

Variant summary

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

The NM_015715.5(PLA2G3):​c.1067-199C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,052 control chromosomes in the GnomAD database, including 23,541 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 0.55 (23541 hom., cov: 33)
• Consequence: PLA2G3 NM_015715.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525

Genes affected

PLA2G3 (HGNC:17934): (phospholipase A2 group III) This gene encodes a protein that belongs to the secreted phospholipase A2 family, whose members include the bee venom enzyme. The encoded enzyme functions in lipid metabolism and catalyzes the calcium-dependent hydrolysis of the sn-2 acyl bond of phospholipids to release arachidonic acid and lysophospholipids. This enzyme acts as a negative regulator of ciliogenesis, and may play a role in cancer development by stimulating tumor cell growth and angiogenesis. This gene is associated with oxidative stress, and polymorphisms in this gene are linked to risk for Alzheimer's disease. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G3	NM_015715.5	c.1067-199C>T		intron_variant		ENST00000215885.4
PLA2G3	XM_011530204.2	c.524-199C>T		intron_variant
PLA2G3	XM_011530205.2	c.524-199C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G3	ENST00000215885.4	c.1067-199C>T		intron_variant		1	NM_015715.5	P1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83998 AN: 151934 Hom.: 23520 Cov.: 33

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.590

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.553 AC: 84074 AN: 152052 Hom.: 23541 Cov.: 33 AF XY: 0.555 AC XY: 41266 AN XY: 74306

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.594

Alfa AF: 0.584 Hom.: 34755

Bravo AF: 0.538

Asia WGS AF: 0.488 AC: 1697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.71
DANN	Benign	0.40

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: rs5753472; hg19: chr22-31533225;