rs5750547

chr22-38150693-G-Achr22-38150693-G-Cchr22-38150693-G-T

Variant summary

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

The NM_003560.4(PLA2G6):c.210-5040C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,128 control chromosomes in the GnomAD database, including 11,494 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 0.38 (11494 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G6	NM_003560.4	c.210-5040C>T		intron_variant		ENST00000332509.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G6	ENST00000332509.8	c.210-5040C>T		intron_variant		1	NM_003560.4	P3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58325 AN: 152006 Hom.: 11470 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.384 AC: 58401 AN: 152124 Hom.: 11494 Cov.: 33 AF XY: 0.387 AC XY: 28806 AN XY: 74364

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.373

Alfa AF: 0.364 Hom.: 9636

Bravo AF: 0.387

Asia WGS AF: 0.423 AC: 1474 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	0.36
Dann	Benign	0.19

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: rs5750547; hg19: chr22-38546700;