rs3890451

Positions:

• chr22-38199813-T-G

Variant summary

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

The ENST00000660610.1(PLA2G6):​c.-42+14640A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 141,868 control chromosomes in the GnomAD database, including 20,867 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 0.54 (20867 hom., cov: 24)
• Consequence: PLA2G6 ENST00000660610.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000594306.1	c.-46+5480A>C		intron_variant		4		ENSP00000473160
PLA2G6	ENST00000660610.1	c.-42+14640A>C		intron_variant				ENSP00000499555	P3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 76165 AN: 141832 Hom.: 20888 Cov.: 24

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.507

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.537 AC: 76154 AN: 141868 Hom.: 20867 Cov.: 24 AF XY: 0.533 AC XY: 36429 AN XY: 68314

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.557

Alfa AF: 0.551 Hom.: 2662

Bravo AF: 0.519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.14

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3890451; hg19: chr22-38595820;