XM_005245891.6:c.-42C>A

Variant names:

• chr1-20068908-C-A
• rs11573185
• ENST00000894073.1:c.-135C>A

Variant summary

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

The XM_005245891.6(PLA2G5):​c.-42C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,281,692 control chromosomes in the GnomAD database, including 179,473 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 0.46 (17261 hom., cov: 31)
  • Exomes 𝑓: 0.53 (162212 hom.)
• Consequence: PLA2G5 XM_005245891.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 7 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: Orphanet, Ambry Genetics, G2P
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000894073.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G5	ENST00000894073.1		c.-135C>A		5_prime_UTR	Exon 3 of 7	ENSP00000564132.1
	PLA2G5	ENST00000894074.1		c.-307C>A		5_prime_UTR	Exon 4 of 9	ENSP00000564133.1
	PLA2G5	ENST00000894075.1		c.-454C>A		5_prime_UTR	Exon 3 of 9	ENSP00000564134.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69409 AN: 151870 Hom.: 17232 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.483

GnomAD2 exomes AF: 0.517 AC: 69057 AN: 133684 AF XY: 0.518

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.591

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.371

Gnomad FIN exome AF: 0.553

Gnomad NFE exome AF: 0.548

Gnomad OTH exome AF: 0.536

GnomAD4 exome AF: 0.532 AC: 600447 AN: 1129704 Hom.: 162212 Cov.: 27 AF XY: 0.532 AC XY: 294959 AN XY: 554636

African (AFR) AF: 0.228 AC: 5536 AN: 24308

American (AMR) AF: 0.592 AC: 16688 AN: 28194

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 7805 AN: 15874

East Asian (EAS) AF: 0.372 AC: 4768 AN: 12808

South Asian (SAS) AF: 0.505 AC: 38389 AN: 75946

European-Finnish (FIN) AF: 0.550 AC: 7190 AN: 13062

Middle Eastern (MID) AF: 0.548 AC: 2405 AN: 4386

European-Non Finnish (NFE) AF: 0.543 AC: 496512 AN: 913810

Other (OTH) AF: 0.512 AC: 21154 AN: 41316

GnomAD4 genome AF: 0.457 AC: 69490 AN: 151988 Hom.: 17261 Cov.: 31 AF XY: 0.457 AC XY: 33940 AN XY: 74272

African (AFR) AF: 0.246 AC: 10196 AN: 41456

American (AMR) AF: 0.557 AC: 8505 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1681 AN: 3470

East Asian (EAS) AF: 0.388 AC: 2002 AN: 5160

South Asian (SAS) AF: 0.481 AC: 2318 AN: 4816

European-Finnish (FIN) AF: 0.533 AC: 5615 AN: 10526

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37371 AN: 67976

Other (OTH) AF: 0.488 AC: 1030 AN: 2112

Alfa AF: 0.516 Hom.: 37477

Bravo AF: 0.451

Asia WGS AF: 0.447 AC: 1555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs11573185; hg19: chr1-20395401; COSMIC: COSV64283089;