Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000371380.8(PLCE1):c.4059C>T(p.Phe1353Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,613,156 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 24 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 11 hom. )

Consequence

PLCE1
ENST00000371380.8 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.408

Publications

2 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=-0.52).

BP6

Variant 10-94265652-C-T is Benign according to our data. Variant chr10-94265652-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.408 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00908 (1380/151916) while in subpopulation AFR AF = 0.0301 (1245/41404). AF 95% confidence interval is 0.0287. There are 24 homozygotes in GnomAd4. There are 658 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 24 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371380.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLCE1	NM_016341.4	MANE Select	c.4059C>T	p.Phe1353Phe	synonymous	Exon 15 of 33	NP_057425.3
PLCE1	NM_001288989.2		c.4011C>T	p.Phe1337Phe	synonymous	Exon 15 of 33	NP_001275918.1
PLCE1	NM_001165979.2		c.3135C>T	p.Phe1045Phe	synonymous	Exon 14 of 32	NP_001159451.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.4059C>T	p.Phe1353Phe	synonymous	Exon 15 of 33	ENSP00000360431.2
PLCE1	ENST00000371375.2	TSL:1	c.3135C>T	p.Phe1045Phe	synonymous	Exon 14 of 31	ENSP00000360426.1
PLCE1	ENST00000692396.1		c.4011C>T	p.Phe1337Phe	synonymous	Exon 15 of 33	ENSP00000508605.1

Frequencies

GnomAD3 genomes

AF:

0.00910

AC:

1381

AN:

151798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00571

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00279

AC:

694

AN:

248896

AF XY:

0.00238

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00301

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000408

Gnomad OTH exome

AF:

0.00232

GnomAD4 exome

AF:

0.00120

AC:

1757

AN:

1461240

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

769

AN XY:

726968

show subpopulations

African (AFR)

AF:

0.0299

AC:

1000

AN:

33464

American (AMR)

AF:

0.00219

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26124

East Asian (EAS)

AF:

0.00131

AC:

AN:

39672

South Asian (SAS)

AF:

0.000928

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000292

AC:

325

AN:

1111502

Other (OTH)

AF:

0.00305

AC:

184

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

174

261

348

435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.00908

AC:

1380

AN:

151916

Hom.:

Cov.:

AF XY:

0.00886

AC XY:

658

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.0301

AC:

1245

AN:

41404

American (AMR)

AF:

0.00570

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00174

AC:

AN:

5174

South Asian (SAS)

AF:

0.000833

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10522

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000324

AC:

AN:

67978

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

135

203

270

338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00371

Hom.:

Bravo

AF:

0.00954

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephrotic syndrome, type 3 (2)

not provided (2)

Focal segmental glomerulosclerosis (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.7

(source)

DANN

Benign

0.63

PhyloP100

-0.41

Mutation Taster

=90/10

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over