rs3736901

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

9 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 links:

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

PLCE1-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_016341.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLCE1	NM_016341.4	MANE Select	c.5035+12C>A	intron	N/A	NP_057425.3
PLCE1	NM_001288989.2		c.4987+12C>A	intron	N/A	NP_001275918.1	B7ZM61
PLCE1	NM_001165979.2		c.4111+12C>A	intron	N/A	NP_001159451.1	Q9P212-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.5035+12C>A	intron	N/A	ENSP00000360431.2	Q9P212-1
PLCE1	ENST00000371375.2	TSL:1	c.4111+12C>A	intron	N/A	ENSP00000360426.1	Q9P212-2
PLCE1	ENST00000875452.1		c.5035+12C>A	intron	N/A	ENSP00000545511.1

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

GnomAD2 exomes

AF:

0.353

AC:

87480

AN:

247582

AF XY:

0.348

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 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

African (AFR)

AF:

0.0592

AC:

1690

AN:

28554

American (AMR)

AF:

0.518

AC:

22957

AN:

44346

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

6924

AN:

24652

East Asian (EAS)

AF:

0.206

AC:

7935

AN:

38516

South Asian (SAS)

AF:

0.275

AC:

22436

AN:

81470

European-Finnish (FIN)

AF:

0.491

AC:

26151

AN:

53244

Middle Eastern (MID)

AF:

0.219

AC:

1144

AN:

5228

European-Non Finnish (NFE)

AF:

0.383

AC:

348156

AN:

908600

Other (OTH)

AF:

0.337

AC:

17812

AN:

52802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

13031

26062

39094

52125

65156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9998

19996

29994

39992

49990

<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:

0.289

AC:

43948

AN:

152000

Hom.:

8085

Cov.:

AF XY:

0.295

AC XY:

21910

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.0705

AC:

2926

AN:

41498

American (AMR)

AF:

0.432

AC:

6591

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

910

AN:

3466

East Asian (EAS)

AF:

0.182

AC:

943

AN:

5172

South Asian (SAS)

AF:

0.259

AC:

1246

AN:

4804

European-Finnish (FIN)

AF:

0.495

AC:

5217

AN:

10532

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.371

AC:

25180

AN:

67954

Other (OTH)

AF:

0.281

AC:

593

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1450

2899

4349

5798

7248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.334

Hom.:

20601

Bravo

AF:

0.276

Asia WGS

AF:

0.197

AC:

682

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephrotic syndrome, type 3 (4)

not provided (3)

not specified (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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

Computational scores

Splicing

Publications

Other links and lift over