22-38167290-C-G

Position:

• chr22-38167290-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.209+1928G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,630 control chromosomes in the GnomAD database, including 1,239 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 0.12 (1239 hom., cov: 31)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.209+1928G>C		intron_variant		ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8	c.209+1928G>C		intron_variant		1	NM_003560.4	ENSP00000333142	P3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17506 AN: 151526 Hom.: 1236 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.116 AC: 17519 AN: 151630 Hom.: 1239 Cov.: 31 AF XY: 0.113 AC XY: 8355 AN XY: 74086

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0809

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0907

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0291 Hom.: 15

Bravo AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.50
DANN	Benign	0.41

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: rs132984; hg19: chr22-38563297;