rs61732522

Positions:

chr10-94252351-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016341.4(PLCE1):c.3132C>T(p.His1044=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00749 in 1,614,042 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 97 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 126 hom. )

Consequence

PLCE1
NM_016341.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 10-94252351-C-T is Benign according to our data. Variant chr10-94252351-C-T is described in ClinVar as [Benign]. Clinvar id is 260717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94252351-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0654 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.3132C>T	p.His1044=	synonymous_variant	9/33	ENST00000371380.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCE1	ENST00000371380.8 linkuse as main transcript	c.3132C>T	p.His1044=	synonymous_variant	9/33	1	NM_016341.4	P1	Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3616

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0673

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0214

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.00467

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.00944

AC:

2354

AN:

249322

Hom.:

AF XY:

0.00867

AC XY:

1172

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.0691

Gnomad AMR exome

AF:

0.00947

Gnomad ASJ exome

AF:

0.00855

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00572

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00533

Gnomad OTH exome

AF:

0.0130

GnomAD4 exome

AF:

0.00578

AC:

8456

AN:

1461816

Hom.:

126

Cov.:

AF XY:

0.00571

AC XY:

4155

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0699

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.00914

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00545

Gnomad4 FIN exome

AF:

0.000449

Gnomad4 NFE exome

AF:

0.00354

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0238

AC:

3626

AN:

152226

Hom.:

Cov.:

AF XY:

0.0236

AC XY:

1756

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0675

Gnomad4 AMR

AF:

0.0214

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00466

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0270

Asia WGS

AF:

0.0130

AC:

AN:

3476

EpiCase

AF:

0.00758

EpiControl

AF:

0.00777

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Nephrotic syndrome, type 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 19, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Focal segmental glomerulosclerosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Sep 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.9

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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