rs1058440

Positions:

• chr2-159983856-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007366.5(PLA2R1):​c.2183+72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 741,284 control chromosomes in the GnomAD database, including 770 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 0.047 (104 hom., cov: 26)
  • Exomes 𝑓: 0.040 (666 hom.)
• Consequence: PLA2R1 NM_007366.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467

Genes affected

PLA2R1 (HGNC:9042): (phospholipase A2 receptor 1) This gene represents a phospholipase A2 receptor. The encoded protein likely exists as both a transmembrane form and a soluble form. The transmembrane receptor may play a role in clearance of phospholipase A2, thereby inhibiting its action. Polymorphisms at this locus have been associated with susceptibility to idiopathic membranous nephropathy. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2R1	NM_007366.5	c.2183+72G>A		intron_variant		ENST00000283243.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2R1	ENST00000283243.13	c.2183+72G>A		intron_variant		1	NM_007366.5	P1
PLA2R1	ENST00000392771.1	c.2183+72G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 4375 AN: 92902 Hom.: 104 Cov.: 26

Gnomad AFR AF: 0.00841

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0473

Gnomad ASJ AF: 0.0517

Gnomad EAS AF: 0.000670

Gnomad SAS AF: 0.0612

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.0165

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.0472

GnomAD4 exome AF: 0.0396 AC: 25685 AN: 648272 Hom.: 666 AF XY: 0.0401 AC XY: 13559 AN XY: 337728

Gnomad4 AFR exome AF: 0.00799

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0320

Gnomad4 EAS exome AF: 0.0000575

Gnomad4 SAS exome AF: 0.0483

Gnomad4 FIN exome AF: 0.0189

Gnomad4 NFE exome AF: 0.0474

Gnomad4 OTH exome AF: 0.0372

GnomAD4 genome AF: 0.0470 AC: 4372 AN: 93012 Hom.: 104 Cov.: 26 AF XY: 0.0466 AC XY: 2111 AN XY: 45340

Gnomad4 AFR AF: 0.00838

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.0517

Gnomad4 EAS AF: 0.000670

Gnomad4 SAS AF: 0.0608

Gnomad4 FIN AF: 0.0366

Gnomad4 NFE AF: 0.0963

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0368 Hom.: 9

Bravo AF: 0.0277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs1058440; hg19: chr2-160840367;