rs147203844

Positions:

• chr10-94234174-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_016341.4(PLCE1):​c.2076A>T​(p.Thr692Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000505 in 1,614,218 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (3 hom.)
• Consequence: PLCE1 NM_016341.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.634

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-94234174-A-T is Benign according to our data. Variant chr10-94234174-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 260714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94234174-A-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.634 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00152 (232/152346) while in subpopulation AFR AF= 0.0039 (162/41586). AF 95% confidence interval is 0.00341. There are 0 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.2076A>T	p.Thr692Thr	synonymous_variant	6/33	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.2076A>T	p.Thr692Thr	synonymous_variant	6/33	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 230 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000697 AC: 174 AN: 249518 Hom.: 0 AF XY: 0.000702 AC XY: 95 AN XY: 135368

Gnomad AFR exome AF: 0.00407

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000915

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.000399 AC: 583 AN: 1461872 Hom.: 3 Cov.: 33 AF XY: 0.000429 AC XY: 312 AN XY: 727234

Gnomad4 AFR exome AF: 0.00526

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000777

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.00152 AC: 232 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74506

Gnomad4 AFR AF: 0.00390

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000467 Hom.: 0

Bravo AF: 0.00177

Asia WGS AF: 0.00376 AC: 14 AN: 3476

EpiCase AF: 0.000436

EpiControl AF: 0.000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:6

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 09, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	PLCE1: BP4, BP7 -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.054
DANN	Benign	0.50

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: rs147203844; hg19: chr10-95993931;