Variant rs3749117 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_007366.5(PLA2R1):c.874A>G(p.Met292Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,590,182 control chromosomes in the GnomAD database, including 171,426 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.36 ( 11993 hom., cov: 32)

Exomes 𝑓: 0.46 ( 159433 hom. )

Consequence

PLA2R1
NM_007366.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.21

Variant links:

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]

PLA2R1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-160028931-T-C is Benign according to our data. Variant chr2-160028931-T-C is described in ClinVar as [Benign]. Clinvar id is 1712439.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2R1	NM_007366.5 linkuse as main transcript	c.874A>G	p.Met292Val	missense_variant	5/30	ENST00000283243.13	NP_031392.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2R1	ENST00000283243.13 linkuse as main transcript	c.874A>G	p.Met292Val	missense_variant	5/30	1	NM_007366.5	ENSP00000283243	P1	Q13018-1
PLA2R1	ENST00000392771.1 linkuse as main transcript	c.874A>G	p.Met292Val	missense_variant	5/27	1		ENSP00000376524		Q13018-2

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54781

AN:

151934

Hom.:

11990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.351

GnomAD3 exomes

AF:

0.390

AC:

97730

AN:

250708

Hom.:

21150

AF XY:

0.392

AC XY:

53178

AN XY:

135498

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.314

Gnomad SAS exome

AF:

0.243

Gnomad FIN exome

AF:

0.510

Gnomad NFE exome

AF:

0.493

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.458

AC:

658404

AN:

1438128

Hom.:

159433

Cov.:

AF XY:

0.452

AC XY:

323950

AN XY:

716418

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.304

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.361

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.506

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.422

GnomAD4 genome

AF:

0.360

AC:

54790

AN:

152054

Hom.:

11993

Cov.:

AF XY:

0.360

AC XY:

26740

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.519

Gnomad4 NFE

AF:

0.499

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.449

Hom.:

30465

Bravo

AF:

0.338

TwinsUK

AF:

0.487

AC:

1806

ALSPAC

AF:

0.508

AC:

1958

ESP6500AA

AF:

0.121

AC:

534

ESP6500EA

AF:

0.490

AC:

4212

ExAC

AF:

0.388

AC:

47079

Asia WGS

AF:

0.320

AC:

1112

AN:

3478

EpiCase

AF:

0.472

EpiControl

AF:

0.466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Atypical hemolytic-uremic syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.039

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

0.79

N;N

REVEL

Benign

0.10

Sift

Benign

0.091

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0020

B;B

Vest4

0.11

MPC

0.067

ClinPred

0.013

GERP RS

4.6

Varity_R

0.15

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.43

Position offset: 32

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over