rs11187870

chr10-94328109-G-Cchr10-94328109-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016341.4(PLCE1):c.*166G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 397,822 control chromosomes in the GnomAD database, including 1,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (467 hom., cov: 33)
  • Exomes 𝑓: 0.075 (971 hom.)
• Consequence: PLCE1 NM_016341.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.53

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]

NOC3L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-94328109-G-C is Benign according to our data. Variant chr10-94328109-G-C is described in ClinVar as [Benign]. Clinvar id is 301737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94328109-G-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCE1	NM_016341.4	c.*166G>C		3_prime_UTR_variant	33/33	ENST00000371380.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCE1	ENST00000371380.8	c.*166G>C		3_prime_UTR_variant	33/33	1	NM_016341.4	P1

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10128 AN: 152162 Hom.: 468 Cov.: 33

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.0850

GnomAD4 exome AF: 0.0753 AC: 18486 AN: 245540 Hom.: 971 Cov.: 0 AF XY: 0.0742 AC XY: 10281 AN XY: 138526

Gnomad4 AFR exome AF: 0.0179

Gnomad4 AMR exome AF: 0.0598

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.0405

Gnomad4 FIN exome AF: 0.0362

Gnomad4 NFE exome AF: 0.0844

Gnomad4 OTH exome AF: 0.0922

GnomAD4 genome AF: 0.0665 AC: 10124 AN: 152282 Hom.: 467 Cov.: 33 AF XY: 0.0632 AC XY: 4709 AN XY: 74452

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0856

Gnomad4 OTH AF: 0.0841

Alfa AF: 0.0731 Hom.: 68

Bravo AF: 0.0690

Asia WGS AF: 0.122 AC: 422 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nephrotic syndrome, type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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. -

Focal segmental glomerulosclerosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Sep 27, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	13
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs11187870; hg19: chr10-96087866;