chr1-20068908-C-A

Position:

• chr1-20068908-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G5	XM_005245891.6	c.-42C>A		5_prime_UTR_variant	4/8		XP_005245948.1
PLA2G5	XM_005245892.6	c.-42C>A		5_prime_UTR_variant	3/7		XP_005245949.1
PLA2G5	XM_005245893.6	c.-307C>A		5_prime_UTR_variant	3/8		XP_005245950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G5	ENST00000460175.5	n.373C>A		non_coding_transcript_exon_variant	3/7	3
PLA2G5	ENST00000465698.5	n.377C>A		non_coding_transcript_exon_variant	3/8	3
PLA2G5	ENST00000469069.5	n.400C>A		non_coding_transcript_exon_variant	4/7	3

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

GnomAD3 exomes AF: 0.517 AC: 69057 AN: 133684 Hom.: 18479 AF XY: 0.518 AC XY: 37674 AN XY: 72780

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 SAS exome AF: 0.510

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

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.372

Gnomad4 SAS exome AF: 0.505

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.512

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

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.488

Alfa AF: 0.525 Hom.: 27275

Bravo AF: 0.451

Asia WGS AF: 0.447 AC: 1555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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