rs2148912

Variant names:

• chr1-20069399-G-A
• rs2148912
• ENST00000460175.5:n.497+367G>A

Variant summary

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

The ENST00000460175.5(PLA2G5):​n.497+367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 152,262 control chromosomes in the GnomAD database, including 490 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 0.062 (490 hom., cov: 32)
• Consequence: PLA2G5 ENST00000460175.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 1 publications found

Genes affected

PLA2G5 (HGNC:9038): (phospholipase A2 group V) This gene is a member of the secretory phospholipase A2 family. It is located in a tightly-linked cluster of secretory phospholipase A2 genes on chromosome 1. The encoded enzyme catalyzes the hydrolysis of membrane phospholipids to generate lysophospholipids and free fatty acids including arachidonic acid. It preferentially hydrolyzes linoleoyl-containing phosphatidylcholine substrates. Secretion of this enzyme is thought to induce inflammatory responses in neighboring cells. Alternatively spliced transcript variants have been found, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

PLA2G5 Gene-Disease associations (from GenCC):

• familial benign flecked retina

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Orphanet
• late-adult onset retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G5	XM_005245891.6	c.83+367G>A		intron_variant	Intron 4 of 7		XP_005245948.1
PLA2G5	XM_005245892.6	c.83+367G>A		intron_variant	Intron 3 of 6		XP_005245949.1
PLA2G5	XM_011541586.4	c.83+367G>A		intron_variant	Intron 2 of 5		XP_011539888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G5	ENST00000460175.5	n.497+367G>A		intron_variant	Intron 3 of 6	3
PLA2G5	ENST00000465698.5	n.501+367G>A		intron_variant	Intron 3 of 7	3
PLA2G5	ENST00000469069.5	n.524+367G>A		intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9512 AN: 152144 Hom.: 493 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0624 AC: 9500 AN: 152262 Hom.: 490 Cov.: 32 AF XY: 0.0673 AC XY: 5007 AN XY: 74448

African (AFR) AF: 0.0215 AC: 894 AN: 41544

American (AMR) AF: 0.110 AC: 1681 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1319 AN: 5186

South Asian (SAS) AF: 0.132 AC: 638 AN: 4826

European-Finnish (FIN) AF: 0.0659 AC: 699 AN: 10612

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0538 AC: 3660 AN: 68022

Other (OTH) AF: 0.0563 AC: 119 AN: 2114

Alfa AF: 0.0532 Hom.: 37

Bravo AF: 0.0631

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.28
DANN	Benign	0.24
PhyloP100		-2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2148912; hg19: chr1-20395892;