rs6757188

Variant names:

• chr2-159987112-T-C
• rs6757188
• NM_007366.5:c.2037+44A>G

Variant summary

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

The NM_007366.5(PLA2R1):​c.2037+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,420,604 control chromosomes in the GnomAD database, including 41,884 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 0.22 (4129 hom., cov: 32)
  • Exomes 𝑓: 0.24 (37755 hom.)
• Consequence: PLA2R1 NM_007366.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2R1	NM_007366.5	c.2037+44A>G		intron_variant	Intron 12 of 29	ENST00000283243.13	NP_031392.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2R1	ENST00000283243.13	c.2037+44A>G		intron_variant	Intron 12 of 29	1	NM_007366.5	ENSP00000283243.7
PLA2R1	ENST00000392771.1	c.2037+44A>G		intron_variant	Intron 12 of 26	1		ENSP00000376524.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33245 AN: 151992 Hom.: 4123 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.271

GnomAD3 exomes AF: 0.256 AC: 63594 AN: 248632 Hom.: 9386 AF XY: 0.250 AC XY: 33599 AN XY: 134418

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.463

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.273

Gnomad SAS exome AF: 0.215

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.237 AC: 300129 AN: 1268494 Hom.: 37755 Cov.: 18 AF XY: 0.236 AC XY: 150832 AN XY: 640314

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.219 AC: 33266 AN: 152110 Hom.: 4129 Cov.: 32 AF XY: 0.216 AC XY: 16055 AN XY: 74360

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.269

Alfa AF: 0.248 Hom.: 1314

Bravo AF: 0.236

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6757188; hg19: chr2-160843623; COSMIC: COSV51779643;