rs17109674

Positions:

Variant summary

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

The NM_016341.4(PLCE1):c.960G>A(p.Glu320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,612,982 control chromosomes in the GnomAD database, including 63,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8727 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54949 hom. )

Consequence

PLCE1
NM_016341.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.640

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=-0.51).

BP6

Variant 10-94032006-G-A is Benign according to our data. Variant chr10-94032006-G-A is described in ClinVar as [Benign]. Clinvar id is 260734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94032006-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCE1	NM_016341.4 linkuse as main transcript	c.960G>A	p.Glu320=	synonymous_variant	2/33	ENST00000371380.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCE1	ENST00000371380.8 linkuse as main transcript	c.960G>A	p.Glu320=	synonymous_variant	2/33	1	NM_016341.4	P1	Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49121

AN:

151848

Hom.:

8723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.290

GnomAD3 exomes

AF:

0.278

AC:

69170

AN:

248926

Hom.:

10635

AF XY:

0.279

AC XY:

37700

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.480

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.429

Gnomad SAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.268

AC:

390989

AN:

1461016

Hom.:

54949

Cov.:

AF XY:

0.268

AC XY:

195095

AN XY:

726830

show subpopulations

Gnomad4 AFR exome

AF:

0.483

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.464

Gnomad4 SAS exome

AF:

0.306

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.323

AC:

49148

AN:

151966

Hom.:

8727

Cov.:

AF XY:

0.325

AC XY:

24121

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.475

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.438

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.282

Hom.:

4472

Bravo

AF:

0.324

Asia WGS

AF:

0.366

AC:

1271

AN:

3476

EpiCase

AF:

0.265

EpiControl

AF:

0.258

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 30% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 28. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Nephrotic syndrome, type 3

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Jul 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 31, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.7

DANN

Benign

0.53

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