rs3788533

Positions:

• chr22-38127239-C-G

Variant summary

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

The NM_003560.4(PLA2G6):​c.1349-790G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,217,292 control chromosomes in the GnomAD database, including 168,259 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 0.47 (17387 hom., cov: 33)
  • Exomes 𝑓: 0.53 (150872 hom.)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75

Genes affected

PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]

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 (SAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G6	NM_003560.4	c.1349-790G>C		intron_variant		ENST00000332509.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G6	ENST00000332509.8	c.1349-790G>C		intron_variant		1	NM_003560.4	P3

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71228 AN: 151910 Hom.: 17388 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.530 AC: 564233 AN: 1065264 Hom.: 150872 Cov.: 33 AF XY: 0.533 AC XY: 273126 AN XY: 512306

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.517

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.469 AC: 71267 AN: 152028 Hom.: 17387 Cov.: 33 AF XY: 0.468 AC XY: 34765 AN XY: 74320

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.491

Alfa AF: 0.479 Hom.: 2206

Bravo AF: 0.465

Asia WGS AF: 0.482 AC: 1680 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	0.35
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3788533; hg19: chr22-38523246;