rs17516758

Positions:

chr10-94298676-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016341.4(PLCE1):c.5458+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,190 control chromosomes in the GnomAD database, including 19,905 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1592 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18313 hom. )

Consequence

PLCE1
NM_016341.4 splice_region, intron

Scores

Splicing: ADA: 0.00006938

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.66

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 (HGNC:):

PLCE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 10-94298676-G-A is Benign according to our data. Variant chr10-94298676-G-A is described in ClinVar as [Benign]. Clinvar id is 260725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94298676-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4 linkuse as main transcript	c.5458+7G>A		splice_region_variant, intron_variant		ENST00000371380.8	NP_057425.3	Q9P212-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8 linkuse as main transcript	c.5458+7G>A		splice_region_variant, intron_variant		1	NM_016341.4	ENSP00000360431.2		Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20966

AN:

151876

Hom.:

1593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0975

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.154

GnomAD3 exomes

AF:

0.137

AC:

34245

AN:

249108

Hom.:

2805

AF XY:

0.144

AC XY:

19406

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.0966

Gnomad AMR exome

AF:

0.0763

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.00184

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.153

AC:

223924

AN:

1461194

Hom.:

18313

Cov.:

AF XY:

0.156

AC XY:

113142

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0949

Gnomad4 AMR exome

AF:

0.0805

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.138

AC:

20961

AN:

151996

Hom.:

1592

Cov.:

AF XY:

0.138

AC XY:

10234

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.0974

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.161

Hom.:

4071

Bravo

AF:

0.129

Asia WGS

AF:

0.0920

AC:

320

AN:

3478

EpiCase

AF:

0.169

EpiControl

AF:

0.168

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 19. Only high quality variants are reported. -

Nephrotic syndrome, type 3

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000069

dbscSNV1_RF

Benign

0.0

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