rs11187870

Variant names:

• chr10-94328109-G-C
• rs11187870
• NM_016341.4:c.*166G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-94328109-G-C
• chr10-94328109-G-T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 1.53
• Publications: 19 publications found

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:24034): (NOC3 like DNA replication regulator) Enables RNA binding activity. Predicted to be involved in DNA replication initiation. Predicted to act upstream of or within fat cell differentiation. Located in mitochondrion; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 301737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.*166G>C		3_prime_UTR_variant	Exon 33 of 33	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.*166G>C		3_prime_UTR_variant	Exon 33 of 33	1	NM_016341.4	ENSP00000360431.2

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

African (AFR) AF: 0.0179 AC: 120 AN: 6718

American (AMR) AF: 0.0598 AC: 1186 AN: 19846

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 1228 AN: 6592

East Asian (EAS) AF: 0.191 AC: 1694 AN: 8848

South Asian (SAS) AF: 0.0405 AC: 1824 AN: 45076

European-Finnish (FIN) AF: 0.0362 AC: 866 AN: 23916

Middle Eastern (MID) AF: 0.145 AC: 315 AN: 2178

European-Non Finnish (NFE) AF: 0.0844 AC: 10242 AN: 121406

Other (OTH) AF: 0.0922 AC: 1011 AN: 10960

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

African (AFR) AF: 0.0167 AC: 694 AN: 41572

American (AMR) AF: 0.0750 AC: 1147 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3466

East Asian (EAS) AF: 0.196 AC: 1013 AN: 5176

South Asian (SAS) AF: 0.0444 AC: 214 AN: 4824

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10612

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0856 AC: 5820 AN: 68020

Other (OTH) AF: 0.0841 AC: 178 AN: 2116

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nephrotic syndrome, type 3 Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Focal segmental glomerulosclerosis Benign:1

Sep 27, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11187870; hg19: chr10-96087866;