1-20039837-T-C

Variant names:

• chr1-20039837-T-C
• rs818678
• ENST00000460175.5:n.276+11128T>C

Variant summary

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

The ENST00000460175.5(PLA2G5):​n.276+11128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,020 control chromosomes in the GnomAD database, including 21,497 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 0.52 (21497 hom., cov: 32)
• Consequence: PLA2G5 ENST00000460175.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 2 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000460175.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G5	ENST00000460175.5	TSL:3	n.276+11128T>C		intron	N/A
	PLA2G5	ENST00000465698.5	TSL:3	n.280+11128T>C		intron	N/A
	PLA2G5	ENST00000469069.5	TSL:3	n.184+11128T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79043 AN: 151902 Hom.: 21486 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.520 AC: 79084 AN: 152020 Hom.: 21497 Cov.: 32 AF XY: 0.515 AC XY: 38254 AN XY: 74314

African (AFR) AF: 0.381 AC: 15776 AN: 41432

American (AMR) AF: 0.458 AC: 6997 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1833 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2051 AN: 5172

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4822

European-Finnish (FIN) AF: 0.601 AC: 6343 AN: 10546

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41942 AN: 67978

Other (OTH) AF: 0.533 AC: 1124 AN: 2108

Alfa AF: 0.529 Hom.: 7559

Bravo AF: 0.504

Asia WGS AF: 0.470 AC: 1634 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.4
DANN	Benign	0.75
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs818678; hg19: chr1-20366330;