rs942676

Positions:

chr10-94316738-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_016341.4(PLCE1):c.6324C>G(p.Val2108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,612,102 control chromosomes in the GnomAD database, including 22,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1569 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20484 hom. )

Consequence

PLCE1
NM_016341.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.41

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:

NOC3L (HGNC:):

NOC3L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 10-94316738-C-G is Benign according to our data. Variant chr10-94316738-C-G is described in ClinVar as [Benign]. Clinvar id is 260729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94316738-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 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.6324C>G	p.Val2108=	synonymous_variant	29/33	ENST00000371380.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCE1	ENST00000371380.8 linkuse as main transcript	c.6324C>G	p.Val2108=	synonymous_variant	29/33	1	NM_016341.4	P1	Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18804

AN:

152048

Hom.:

1570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0300

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.0789

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.146

AC:

36403

AN:

249302

Hom.:

3202

AF XY:

0.147

AC XY:

19920

AN XY:

135262

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.0767

Gnomad EAS exome

AF:

0.000723

Gnomad SAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.137

GnomAD4 exome

AF:

0.160

AC:

233965

AN:

1459936

Hom.:

20484

Cov.:

AF XY:

0.160

AC XY:

116043

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.0225

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.0782

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.124

AC:

18801

AN:

152166

Hom.:

1569

Cov.:

AF XY:

0.125

AC XY:

9310

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0299

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.0789

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.146

Hom.:

602

Bravo

AF:

0.111

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

EpiCase

AF:

0.154

EpiControl

AF:

0.152

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 37% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 34. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

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

-0.40

CADD

Benign

5.6

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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