chr16-68247408-T-C

Variant names:

• chr16-68247408-T-C
• rs10500543
• NM_012320.4:c.127+1855T>C

Variant summary

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

The NM_012320.4(PLA2G15):​c.127+1855T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,206 control chromosomes in the GnomAD database, including 991 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 (991 hom., cov: 32)
• Consequence: PLA2G15 NM_012320.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 4 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=-0.86).
• 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.127+1855T>C		intron_variant	Intron 1 of 5	ENST00000219345.10	NP_036452.1
PLA2G15	NM_001363551.2	c.127+1855T>C		intron_variant	Intron 1 of 5		NP_001350480.1
PLA2G15	XM_011522979.3	c.127+1855T>C		intron_variant	Intron 1 of 6		XP_011521281.1
PLA2G15	XM_011522980.4	c.127+1855T>C		intron_variant	Intron 1 of 6		XP_011521282.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G15	ENST00000219345.10	c.127+1855T>C		intron_variant	Intron 1 of 5	1	NM_012320.4	ENSP00000219345.5

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16193 AN: 152088 Hom.: 989 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.106 AC: 16201 AN: 152206 Hom.: 991 Cov.: 32 AF XY: 0.111 AC XY: 8296 AN XY: 74406

African (AFR) AF: 0.0558 AC: 2318 AN: 41522

American (AMR) AF: 0.128 AC: 1962 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3470

East Asian (EAS) AF: 0.106 AC: 547 AN: 5178

South Asian (SAS) AF: 0.197 AC: 953 AN: 4826

European-Finnish (FIN) AF: 0.153 AC: 1619 AN: 10608

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

European-Non Finnish (NFE) AF: 0.114 AC: 7743 AN: 67996

Other (OTH) AF: 0.126 AC: 266 AN: 2114

Alfa AF: 0.107 Hom.: 115

Bravo AF: 0.102

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.53
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10500543; hg19: chr16-68281311;