rs3761447

chr22-38199532-G-A

Variant summary

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

The ENST00000660610.1(PLA2G6):c.-42+14921C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,474 control chromosomes in the GnomAD database, including 18,221 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 (18221 hom., cov: 29)
• Consequence: PLA2G6 ENST00000660610.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G6	ENST00000594306.1	c.-46+5761C>T		intron_variant		4
PLA2G6	ENST00000660610.1	c.-42+14921C>T		intron_variant				P3

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71030 AN: 151356 Hom.: 18232 Cov.: 29

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.469 AC: 71038 AN: 151474 Hom.: 18221 Cov.: 29 AF XY: 0.469 AC XY: 34693 AN XY: 73918

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.487

Alfa AF: 0.513 Hom.: 2638

Bravo AF: 0.457

Asia WGS AF: 0.455 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.70
Dann	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3761447; hg19: chr22-38595539;