rs9935022

Positions:

• chr16-68245376-A-T

Variant summary

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

The NM_012320.4(PLA2G15):​c.-51A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00934 in 1,582,552 control chromosomes in the GnomAD database, including 753 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 0.040 (378 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (375 hom.)
• Consequence: PLA2G15 NM_012320.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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]

PLA2G15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G15	NM_012320.4	c.-51A>T		5_prime_UTR_variant	1/6	ENST00000219345.10	NP_036452.1
PLA2G15	NM_001363551.2	c.-51A>T		5_prime_UTR_variant	1/6		NP_001350480.1
PLA2G15	XM_011522979.3	c.-51A>T		5_prime_UTR_variant	1/7		XP_011521281.1
PLA2G15	XM_011522980.4	c.-51A>T		5_prime_UTR_variant	1/7		XP_011521282.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G15	ENST00000219345	c.-51A>T		5_prime_UTR_variant	1/6	1	NM_012320.4	ENSP00000219345.5

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6105 AN: 152110 Hom.: 374 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.0307

GnomAD3 exomes AF: 0.0117 AC: 2674 AN: 228658 Hom.: 139 AF XY: 0.00908 AC XY: 1139 AN XY: 125448

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.00893

Gnomad ASJ exome AF: 0.00873

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000269

Gnomad FIN exome AF: 0.00252

Gnomad NFE exome AF: 0.00215

Gnomad OTH exome AF: 0.00667

GnomAD4 exome AF: 0.00605 AC: 8659 AN: 1430324 Hom.: 375 Cov.: 31 AF XY: 0.00550 AC XY: 3905 AN XY: 710020

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.0100

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.000469

Gnomad4 FIN exome AF: 0.00252

Gnomad4 NFE exome AF: 0.00201

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0402 AC: 6124 AN: 152228 Hom.: 378 Cov.: 32 AF XY: 0.0387 AC XY: 2883 AN XY: 74442

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00231

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0236 Hom.: 25

Bravo AF: 0.0449

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.6
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9935022; hg19: chr16-68279279;