Variant rs3740360 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016341.4(PLCE1):c.4115+26A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,613,394 control chromosomes in the GnomAD database, including 10,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.086 ( 715 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9286 hom. )

Consequence

PLCE1
NM_016341.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.22

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-94265734-A-C is Benign according to our data. Variant chr10-94265734-A-C is described in ClinVar as [Benign]. Clinvar id is 1296591.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCE1	NM_016341.4 linkuse as main transcript	c.4115+26A>C		intron_variant		ENST00000371380.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCE1	ENST00000371380.8 linkuse as main transcript	c.4115+26A>C		intron_variant		1	NM_016341.4	P1	Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.0863

AC:

13120

AN:

152094

Hom.:

716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0876

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.0449

Gnomad FIN

AF:

0.0730

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.0956

GnomAD3 exomes

AF:

0.0974

AC:

24269

AN:

249096

Hom.:

1457

AF XY:

0.0985

AC XY:

13314

AN XY:

135116

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.0650

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.184

Gnomad SAS exome

AF:

0.0409

Gnomad FIN exome

AF:

0.0715

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.107

AC:

156353

AN:

1461182

Hom.:

9286

Cov.:

AF XY:

0.107

AC XY:

77440

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.0237

Gnomad4 AMR exome

AF:

0.0686

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.0411

Gnomad4 FIN exome

AF:

0.0705

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.0862

AC:

13119

AN:

152212

Hom.:

715

Cov.:

AF XY:

0.0839

AC XY:

6244

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0233

Gnomad4 AMR

AF:

0.0875

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.0447

Gnomad4 FIN

AF:

0.0730

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.0946

Alfa

AF:

0.100

Hom.:

577

Bravo

AF:

0.0861

Asia WGS

AF:

0.120

AC:

418

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.55

DANN

Benign

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over