rs17109674

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.960G>A(p.Glu320Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,612,982 control chromosomes in the GnomAD database, including 63,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8727 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54949 hom. )

Consequence

PLCE1
NM_016341.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.640

Publications

20 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=-0.51).

BP6

Variant 10-94032006-G-A is Benign according to our data. Variant chr10-94032006-G-A is described in ClinVar as Benign. ClinVar VariationId is 260734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016341.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	NM_016341.4	MANE Select	c.960G>A	p.Glu320Glu	synonymous	Exon 2 of 33	NP_057425.3
	PLCE1	NM_001288989.2		c.960G>A	p.Glu320Glu	synonymous	Exon 2 of 33	NP_001275918.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.960G>A	p.Glu320Glu	synonymous	Exon 2 of 33	ENSP00000360431.2
PLCE1	ENST00000692396.1		c.960G>A	p.Glu320Glu	synonymous	Exon 2 of 33	ENSP00000508605.1
PLCE1	ENST00000692286.1		c.960G>A	p.Glu320Glu	synonymous	Exon 1 of 30	ENSP00000509490.1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49121

AN:

151848

Hom.:

8723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.290

GnomAD2 exomes

AF:

0.278

AC:

69170

AN:

248926

AF XY:

0.279

show subpopulations

Gnomad AFR exome

AF:

0.480

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.268

AC:

390989

AN:

1461016

Hom.:

54949

Cov.:

AF XY:

0.268

AC XY:

195095

AN XY:

726830

show subpopulations

African (AFR)

AF:

0.483

AC:

16163

AN:

33438

American (AMR)

AF:

0.161

AC:

7215

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

6709

AN:

26120

East Asian (EAS)

AF:

0.464

AC:

18427

AN:

39686

South Asian (SAS)

AF:

0.306

AC:

26415

AN:

86226

European-Finnish (FIN)

AF:

0.287

AC:

15309

AN:

53408

Middle Eastern (MID)

AF:

0.231

AC:

1332

AN:

5760

European-Non Finnish (NFE)

AF:

0.254

AC:

282465

AN:

1111328

Other (OTH)

AF:

0.281

AC:

16954

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15543

31085

46628

62170

77713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9764

19528

29292

39056

48820

<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:

0.323

AC:

49148

AN:

151966

Hom.:

8727

Cov.:

AF XY:

0.325

AC XY:

24121

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.475

AC:

19693

AN:

41454

American (AMR)

AF:

0.225

AC:

3435

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

850

AN:

3464

East Asian (EAS)

AF:

0.438

AC:

2254

AN:

5142

South Asian (SAS)

AF:

0.315

AC:

1516

AN:

4812

European-Finnish (FIN)

AF:

0.305

AC:

3224

AN:

10562

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17287

AN:

67968

Other (OTH)

AF:

0.289

AC:

610

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1638

3277

4915

6554

8192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.288

Hom.:

6919

Bravo

AF:

0.324

Asia WGS

AF:

0.366

AC:

1271

AN:

3476

EpiCase

AF:

0.265

EpiControl

AF:

0.258

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Nephrotic syndrome, type 3 (3)

not specified (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.7

(source)

DANN

Benign

0.53

PhyloP100

0.64

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

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