rs3736901

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016341.4(PLCE1):c.5035+12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,389,412 control chromosomes in the GnomAD database, including 95,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8085 hom., cov: 32)

Exomes 𝑓: 0.37 ( 87196 hom. )

Consequence

PLCE1
NM_016341.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.14

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:

PLCE1-AS1 (HGNC:45193): (PLCE1 antisense RNA 1)

PLCE1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 10-94284977-C-A is Benign according to our data. Variant chr10-94284977-C-A is described in ClinVar as [Benign]. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4 link	c.5035+12C>A		intron_variant	Intron 22 of 32	ENST00000371380.8	NP_057425.3	Q9P212-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8 link	c.5035+12C>A		intron_variant	Intron 22 of 32	1	NM_016341.4	ENSP00000360431.2		Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43924

AN:

151882

Hom.:

8073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0707

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.282

GnomAD3 exomes

AF:

0.353

AC:

87480

AN:

247582

Hom.:

17534

AF XY:

0.348

AC XY:

46710

AN XY:

134344

show subpopulations

Gnomad AFR exome

AF:

0.0634

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.374

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.368

AC:

455205

AN:

1237412

Hom.:

87196

Cov.:

AF XY:

0.363

AC XY:

228023

AN XY:

627404

show subpopulations

Gnomad4 AFR exome

AF:

0.0592

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.281

Gnomad4 EAS exome

AF:

0.206

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.491

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.289

AC:

43948

AN:

152000

Hom.:

8085

Cov.:

AF XY:

0.295

AC XY:

21910

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0705

Gnomad4 AMR

AF:

0.432

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.259

Gnomad4 FIN

AF:

0.495

Gnomad4 NFE

AF:

0.371

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.347

Hom.:

13967

Bravo

AF:

0.276

Asia WGS

AF:

0.197

AC:

682

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 3

Benign:4

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 59. Only high quality variants are reported. -

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.61

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