dbSNP rs1858610: PLCE1:c.4795+726G>A (chr10-94280637-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016341.4(PLCE1):c.4795+726G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,072 control chromosomes in the GnomAD database, including 9,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 9076 hom., cov: 32)

Exomes 𝑓: 0.20 ( 0 hom. )

Consequence

PLCE1
NM_016341.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.920

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 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.4795+726G>A	intron	N/A	NP_057425.3
PLCE1	NM_001288989.2		c.4747+726G>A	intron	N/A	NP_001275918.1	B7ZM61
PLCE1	NM_001165979.2		c.3871+726G>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.4795+726G>A	intron	N/A	ENSP00000360431.2	Q9P212-1
PLCE1	ENST00000371375.2	TSL:1	c.3871+726G>A	intron	N/A	ENSP00000360426.1	Q9P212-2
PLCE1	ENST00000875452.1		c.4795+726G>A	intron	N/A	ENSP00000545511.1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52143

AN:

151900

Hom.:

9069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.363

GnomAD4 exome

AF:

0.204

AC:

AN:

Hom.:

Cov.:

AF XY:

0.188

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.208

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.343

AC:

52169

AN:

152018

Hom.:

9076

Cov.:

AF XY:

0.341

AC XY:

25367

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.401

AC:

16610

AN:

41450

American (AMR)

AF:

0.296

AC:

4510

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1256

AN:

3468

East Asian (EAS)

AF:

0.340

AC:

1757

AN:

5168

South Asian (SAS)

AF:

0.378

AC:

1823

AN:

4822

European-Finnish (FIN)

AF:

0.258

AC:

2725

AN:

10552

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.327

AC:

22219

AN:

67976

Other (OTH)

AF:

0.361

AC:

763

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1797

3595

5392

7190

8987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.341

Hom.:

1786

Bravo

AF:

0.348

Asia WGS

AF:

0.349

AC:

1215

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.2

(source)

DANN

Benign

0.60

PhyloP100

0.92

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over