chr1-20082881-A-C

Variant names:

• chr1-20082881-A-C
• rs525380
• NM_000929.3:c.-10-1940A>C

Variant summary

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

The NM_000929.3(PLA2G5):​c.-10-1940A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,818 control chromosomes in the GnomAD database, including 23,782 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 0.56 (23782 hom., cov: 33)
• Consequence: PLA2G5 NM_000929.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G5	NM_000929.3	c.-10-1940A>C		intron_variant	Intron 1 of 4	ENST00000375108.4	NP_000920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G5	ENST00000375108.4	c.-10-1940A>C		intron_variant	Intron 1 of 4	1	NM_000929.3	ENSP00000364249.3

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84165 AN: 151698 Hom.: 23737 Cov.: 33

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.555 AC: 84274 AN: 151818 Hom.: 23782 Cov.: 33 AF XY: 0.557 AC XY: 41327 AN XY: 74244

African (AFR) AF: 0.516 AC: 21233 AN: 41166

American (AMR) AF: 0.606 AC: 9253 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2261 AN: 3472

East Asian (EAS) AF: 0.575 AC: 2973 AN: 5172

South Asian (SAS) AF: 0.550 AC: 2652 AN: 4826

European-Finnish (FIN) AF: 0.556 AC: 5877 AN: 10578

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37965 AN: 68010

Other (OTH) AF: 0.598 AC: 1261 AN: 2110

Alfa AF: 0.559 Hom.: 32810

Bravo AF: 0.555

Asia WGS AF: 0.589 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.0
DANN	Benign	0.63
PhyloP100		0.12
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: rs525380; hg19: chr1-20409374;