rs41291134

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000371380.8(PLCE1):c.4263G>A(p.Ser1421=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,613,768 control chromosomes in the GnomAD database, including 1,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 326 hom., cov: 32)

Exomes 𝑓: 0.027 ( 797 hom. )

Consequence

PLCE1
ENST00000371380.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.352

Variant links:

Genes affected

PLCE1 (HGNC:17175): (phospholipase C epsilon 1) This gene encodes a phospholipase enzyme that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers subsequently regulate various processes affecting cell growth, differentiation, and gene expression. This enzyme is regulated by small monomeric GTPases of the Ras and Rho families and by heterotrimeric G proteins. In addition to its phospholipase C catalytic activity, this enzyme has an N-terminal domain with guanine nucleotide exchange (GEF) activity. Mutations in this gene cause early-onset nephrotic syndrome; characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

PLCE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 10-94265940-G-A is Benign according to our data. Variant chr10-94265940-G-A is described in ClinVar as [Benign]. Clinvar id is 260719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94265940-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.352 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4 linkuse as main transcript	c.4263G>A	p.Ser1421=	synonymous_variant	16/33	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8 linkuse as main transcript	c.4263G>A	p.Ser1421=	synonymous_variant	16/33	1	NM_016341.4	ENSP00000360431	P1	Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.0512

AC:

7786

AN:

151976

Hom.:

324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0393

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.0485

Gnomad FIN

AF:

0.00795

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0231

Gnomad OTH

AF:

0.0623

GnomAD3 exomes

AF:

0.0324

AC:

8069

AN:

249280

Hom.:

212

AF XY:

0.0326

AC XY:

4403

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.0191

Gnomad ASJ exome

AF:

0.0139

Gnomad EAS exome

AF:

0.0422

Gnomad SAS exome

AF:

0.0500

Gnomad FIN exome

AF:

0.00942

Gnomad NFE exome

AF:

0.0241

Gnomad OTH exome

AF:

0.0334

GnomAD4 exome

AF:

0.0265

AC:

38770

AN:

1461674

Hom.:

797

Cov.:

AF XY:

0.0271

AC XY:

19701

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.0218

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.0360

Gnomad4 SAS exome

AF:

0.0506

Gnomad4 FIN exome

AF:

0.00844

Gnomad4 NFE exome

AF:

0.0222

Gnomad4 OTH exome

AF:

0.0335

GnomAD4 genome

AF:

0.0513

AC:

7800

AN:

152094

Hom.:

326

Cov.:

AF XY:

0.0506

AC XY:

3765

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.0393

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.0363

Gnomad4 SAS

AF:

0.0486

Gnomad4 FIN

AF:

0.00795

Gnomad4 NFE

AF:

0.0231

Gnomad4 OTH

AF:

0.0607

Alfa

AF:

0.0344

Hom.:

106

Bravo

AF:

0.0564

Asia WGS

AF:

0.0500

AC:

175

AN:

3476

EpiCase

AF:

0.0244

EpiControl

AF:

0.0273

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 11, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Nephrotic syndrome, type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.3

DANN

Benign

0.55

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

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