rs17688076

Variant names:

• chr16-68252524-C-A
• rs17688076
• NM_012320.4:c.285-2395C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012320.4(PLA2G15):​c.285-2395C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 455,970 control chromosomes in the GnomAD database, including 4,279 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 0.11 (1005 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3274 hom.)
• Consequence: PLA2G15 NM_012320.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G15	NM_012320.4	c.285-2395C>A		intron_variant	Intron 2 of 5	ENST00000219345.10	NP_036452.1
PLA2G15	NM_001363551.2	c.285-2395C>A		intron_variant	Intron 2 of 5		NP_001350480.1
PLA2G15	XM_011522979.3	c.285-898C>A		intron_variant	Intron 2 of 6		XP_011521281.1
PLA2G15	XM_011522980.4	c.285-898C>A		intron_variant	Intron 2 of 6		XP_011521282.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G15	ENST00000219345.10	c.285-2395C>A		intron_variant	Intron 2 of 5	1	NM_012320.4	ENSP00000219345.5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16481 AN: 152142 Hom.: 1001 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.139 AC: 17820 AN: 127854 AF XY: 0.142

Gnomad AFR exome AF: 0.0604

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.138 AC: 42046 AN: 303710 Hom.: 3274 Cov.: 0 AF XY: 0.143 AC XY: 24800 AN XY: 172956

African (AFR) AF: 0.0606 AC: 522 AN: 8620

American (AMR) AF: 0.150 AC: 4099 AN: 27254

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 1759 AN: 10786

East Asian (EAS) AF: 0.115 AC: 1061 AN: 9208

South Asian (SAS) AF: 0.200 AC: 11956 AN: 59726

European-Finnish (FIN) AF: 0.147 AC: 1825 AN: 12374

Middle Eastern (MID) AF: 0.120 AC: 332 AN: 2776

European-Non Finnish (NFE) AF: 0.118 AC: 18689 AN: 158750

Other (OTH) AF: 0.127 AC: 1803 AN: 14216

GnomAD4 genome AF: 0.108 AC: 16504 AN: 152260 Hom.: 1005 Cov.: 32 AF XY: 0.113 AC XY: 8444 AN XY: 74426

African (AFR) AF: 0.0629 AC: 2612 AN: 41558

American (AMR) AF: 0.129 AC: 1980 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3472

East Asian (EAS) AF: 0.105 AC: 542 AN: 5182

South Asian (SAS) AF: 0.197 AC: 950 AN: 4818

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10606

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7740 AN: 68016

Other (OTH) AF: 0.127 AC: 269 AN: 2112

Alfa AF: 0.116 Hom.: 200

Bravo AF: 0.105

Asia WGS AF: 0.189 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.1
DANN	Benign	0.76
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17688076; hg19: chr16-68286427; COSMIC: COSV54723276; COSMIC: COSV54723276;