rs17109671

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

nephrotic syndrome, type 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PLCE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 260733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PLCE1	NM_016341.4 link	c.810T>C	p.Cys270Cys	synonymous_variant	Exon 2 of 33	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8 link	c.810T>C	p.Cys270Cys	synonymous_variant	Exon 2 of 33	1	NM_016341.4	ENSP00000360431.2

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

GnomAD2 exomes

AF:

0.310

AC:

77151

AN:

248700

AF XY:

0.307

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 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

African (AFR)

AF:

0.727

AC:

24314

AN:

33456

American (AMR)

AF:

0.211

AC:

9447

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

7904

AN:

26120

East Asian (EAS)

AF:

0.499

AC:

19810

AN:

39680

South Asian (SAS)

AF:

0.317

AC:

27300

AN:

86240

European-Finnish (FIN)

AF:

0.287

AC:

15333

AN:

53404

Middle Eastern (MID)

AF:

0.274

AC:

1583

AN:

5768

European-Non Finnish (NFE)

AF:

0.263

AC:

292202

AN:

1111606

Other (OTH)

AF:

0.313

AC:

18883

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

17095

34191

51286

68382

85477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10140

20280

30420

40560

50700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.401

AC:

60902

AN:

151972

Hom.:

15101

Cov.:

AF XY:

0.399

AC XY:

29650

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.708

AC:

29363

AN:

41460

American (AMR)

AF:

0.279

AC:

4256

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1012

AN:

3472

East Asian (EAS)

AF:

0.476

AC:

2456

AN:

5156

South Asian (SAS)

AF:

0.326

AC:

1572

AN:

4816

European-Finnish (FIN)

AF:

0.306

AC:

3235

AN:

10556

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17952

AN:

67948

Other (OTH)

AF:

0.360

AC:

760

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1579

3158

4737

6316

7895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.326

Hom.:

6884

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 31, 2017

Athena Diagnostics

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

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

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 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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephrotic syndrome, type 3

Benign:3

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. -

Jul 28, 2017

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.7

(source)

DANN

Benign

0.41

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over