chr10-94279951-C-T

Variant names:

Variant summary

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

The NM_016341.4(PLCE1):c.4795+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,606,320 control chromosomes in the GnomAD database, including 70,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5798 hom., cov: 32)

Exomes 𝑓: 0.30 ( 64620 hom. )

Consequence

PLCE1
NM_016341.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.125

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:

PLCE1-AS1 (HGNC:45193): (PLCE1 antisense RNA 1)

PLCE1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-94279951-C-T is Benign according to our data. Variant chr10-94279951-C-T is described in ClinVar as [Benign]. Clinvar id is 1286352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4 link	c.4795+40C>T		intron_variant	Intron 20 of 32	ENST00000371380.8	NP_057425.3	Q9P212-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8 link	c.4795+40C>T		intron_variant	Intron 20 of 32	1	NM_016341.4	ENSP00000360431.2		Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41679

AN:

151938

Hom.:

5804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.291

AC:

72168

AN:

248402

Hom.:

10704

AF XY:

0.294

AC XY:

39653

AN XY:

134826

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.320

Gnomad SAS exome

AF:

0.334

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.296

AC:

431170

AN:

1454264

Hom.:

64620

Cov.:

AF XY:

0.298

AC XY:

216018

AN XY:

723980

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.247

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.298

GnomAD4 genome

AF:

0.274

AC:

41678

AN:

152056

Hom.:

5798

Cov.:

AF XY:

0.273

AC XY:

20311

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.245

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.339

Gnomad4 FIN

AF:

0.250

Gnomad4 NFE

AF:

0.301

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.295

Hom.:

2963

Bravo

AF:

0.272

Asia WGS

AF:

0.286

AC:

996

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

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 35% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.1

DANN

Benign

0.53

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