10-94031856-T-C

Position:

chr10-94031856-T-C

Variant summary

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

The NM_016341.4(PLCE1):c.810T>C(p.Cys270Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,613,324 control chromosomes in the GnomAD database, including 79,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 15101 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64853 hom. )

Consequence

PLCE1
NM_016341.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.211

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 (HGNC:):

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=-0.85).

BP6

Variant 10-94031856-T-C is Benign according to our data. Variant chr10-94031856-T-C is described in ClinVar as [Benign]. Clinvar id is 260733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94031856-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.211 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 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.810T>C	p.Cys270Cys	synonymous_variant	2/33	ENST00000371380.8	NP_057425.3	Q9P212-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8 linkuse as main transcript	c.810T>C	p.Cys270Cys	synonymous_variant	2/33	1	NM_016341.4	ENSP00000360431.2		Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60817

AN:

151852

Hom.:

15063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.708

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.299

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.361

GnomAD3 exomes

AF:

0.310

AC:

77151

AN:

248700

Hom.:

13955

AF XY:

0.307

AC XY:

41389

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.716

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.465

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.275

GnomAD4 exome

AF:

0.285

AC:

416776

AN:

1461352

Hom.:

64853

Cov.:

AF XY:

0.285

AC XY:

207126

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.499

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.401

AC:

60902

AN:

151972

Hom.:

15101

Cov.:

AF XY:

0.399

AC XY:

29650

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.708

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.291

Gnomad4 EAS

AF:

0.476

Gnomad4 SAS

AF:

0.326

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.360

Alfa

AF:

0.317

Hom.:

4989

Bravo

AF:

0.414

Asia WGS

AF:

0.398

AC:

1385

AN:

3478

EpiCase

AF:

0.278

EpiControl

AF:

0.272

ClinVar

Significance: Benign

Submissions summary: Benign:10

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 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 31, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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 40% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 37. Only high quality variants are reported. -

Nephrotic syndrome, type 3

Benign:3

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.7

DANN

Benign

0.41

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