rs949753

Variant names:

• chr2-159954673-A-G
• rs949753
• NM_007366.5:c.3301+526T>C

Variant summary

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

The NM_007366.5(PLA2R1):​c.3301+526T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,016 control chromosomes in the GnomAD database, including 2,808 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 0.18 (2808 hom., cov: 31)
• Consequence: PLA2R1 NM_007366.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2R1	NM_007366.5	c.3301+526T>C		intron_variant	Intron 23 of 29	ENST00000283243.13	NP_031392.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2R1	ENST00000283243.13	c.3301+526T>C		intron_variant	Intron 23 of 29	1	NM_007366.5	ENSP00000283243.7
PLA2R1	ENST00000392771.1	c.3301+526T>C		intron_variant	Intron 23 of 26	1		ENSP00000376524.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27539 AN: 151898 Hom.: 2814 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.181 AC: 27538 AN: 152016 Hom.: 2808 Cov.: 31 AF XY: 0.186 AC XY: 13832 AN XY: 74296

African (AFR) AF: 0.102 AC: 4212 AN: 41484

American (AMR) AF: 0.172 AC: 2628 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 914 AN: 3466

East Asian (EAS) AF: 0.180 AC: 929 AN: 5168

South Asian (SAS) AF: 0.421 AC: 2026 AN: 4814

European-Finnish (FIN) AF: 0.201 AC: 2125 AN: 10574

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14045 AN: 67944

Other (OTH) AF: 0.194 AC: 410 AN: 2110

Alfa AF: 0.198 Hom.: 8870

Bravo AF: 0.170

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		0.052
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: rs949753; hg19: chr2-160811184;