Variant chr10-94030912-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016341.4(PLCE1):c.-135G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 850,334 control chromosomes in the GnomAD database, including 35,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8116 hom., cov: 32)

Exomes 𝑓: 0.27 ( 27797 hom. )

Consequence

PLCE1
NM_016341.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.140

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-94030912-G-A is Benign according to our data. Variant chr10-94030912-G-A is described in ClinVar as [Benign]. Clinvar id is 301676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94030912-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 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.-135G>A		5_prime_UTR_variant	2/33	ENST00000371380.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCE1	ENST00000371380.8 linkuse as main transcript	c.-135G>A		5_prime_UTR_variant	2/33	1	NM_016341.4	P1	Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47769

AN:

151894

Hom.:

8111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.437

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.274

AC:

191034

AN:

698322

Hom.:

27797

Cov.:

AF XY:

0.275

AC XY:

102490

AN XY:

373362

show subpopulations

Gnomad4 AFR exome

AF:

0.437

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.244

Gnomad4 EAS exome

AF:

0.467

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.285

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.314

AC:

47790

AN:

152012

Hom.:

8116

Cov.:

AF XY:

0.316

AC XY:

23485

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.444

Gnomad4 AMR

AF:

0.222

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.437

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.264

Hom.:

5387

Bravo

AF:

0.313

Asia WGS

AF:

0.362

AC:

1258

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

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

-0.81

CADD

Benign

3.7

DANN

Benign

0.54

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