16-68251944-A-G

Position:

• chr16-68251944-A-G

Variant summary

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

The NM_012320.4(PLA2G15):​c.284+2498A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 150,518 control chromosomes in the GnomAD database, including 6,130 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 0.25 (6130 hom., cov: 31)
• Consequence: PLA2G15 NM_012320.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

PLA2G15 (HGNC:17163): (phospholipase A2 group XV) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. The protein encoded by this gene hydrolyzes lysophosphatidylcholine to glycerophosphorylcholine and a free fatty acid. This enzyme is present in the plasma and thought to be associated with high-density lipoprotein. A later paper contradicts the function of this gene. It demonstrates that this gene encodes a lysosomal enzyme instead of a lysophospholipase and has both calcium-independent phospholipase A2 and transacylase activities. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G15	NM_012320.4	c.284+2498A>G		intron_variant		ENST00000219345.10
PLA2G15	NM_001363551.2	c.284+2498A>G		intron_variant
PLA2G15	XM_011522979.3	c.285-1478A>G		intron_variant
PLA2G15	XM_011522980.4	c.285-1478A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G15	ENST00000219345.10	c.284+2498A>G		intron_variant		1	NM_012320.4	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38219 AN: 150422 Hom.: 6101 Cov.: 31

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.254 AC: 38302 AN: 150518 Hom.: 6130 Cov.: 31 AF XY: 0.256 AC XY: 18743 AN XY: 73340

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.259

Alfa AF: 0.191 Hom.: 1478

Bravo AF: 0.262

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.52
DANN	Benign	0.34

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: rs1975802; hg19: chr16-68285847;