rs17109671

Variant names:

• chr10-94031856-T-C
• rs17109671
• NM_016341.4:c.810T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016341.4(PLCE1):​c.810T>C​(p.Cys270Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,613,324 control chromosomes in the GnomAD database, including 79,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (15101 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64853 hom.)
• Consequence: PLCE1 NM_016341.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.211

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-94031856-T-C is Benign according to our data. Variant chr10-94031856-T-C is described in ClinVar as [Benign]. Clinvar id is 260733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94031856-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.211 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.810T>C	p.Cys270Cys	synonymous_variant	Exon 2 of 33	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.810T>C	p.Cys270Cys	synonymous_variant	Exon 2 of 33	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60817 AN: 151852 Hom.: 15063 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.361

GnomAD3 exomes AF: 0.310 AC: 77151 AN: 248700 Hom.: 13955 AF XY: 0.307 AC XY: 41389 AN XY: 134884

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.303

Gnomad EAS exome AF: 0.465

Gnomad SAS exome AF: 0.320

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.285 AC: 416776 AN: 1461352 Hom.: 64853 Cov.: 36 AF XY: 0.285 AC XY: 207126 AN XY: 726968

Gnomad4 AFR exome AF: 0.727

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.499

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.401 AC: 60902 AN: 151972 Hom.: 15101 Cov.: 32 AF XY: 0.399 AC XY: 29650 AN XY: 74272

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.360

Alfa AF: 0.317 Hom.: 4989

Bravo AF: 0.414

Asia WGS AF: 0.398 AC: 1385 AN: 3478

EpiCase AF: 0.278

EpiControl AF: 0.272

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Mar 31, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:3

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 37. Only high quality variants are reported. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nephrotic syndrome, type 3 Benign:3

Jan 13, 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. -

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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 28, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

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	-0.85
CADD	Benign	2.7
DANN	Benign	0.41

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: rs17109671; hg19: chr10-95791613; COSMIC: COSV53354951;