Variant 10-94283975-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016341.4(PLCE1):c.4917+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,572,808 control chromosomes in the GnomAD database, including 75,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8702 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66648 hom. )

Consequence

PLCE1
NM_016341.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.783

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 10-94283975-A-G is Benign according to our data. Variant chr10-94283975-A-G is described in ClinVar as [Benign]. Clinvar id is 1235235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4 linkuse as main transcript	c.4917+64A>G		intron_variant		ENST00000371380.8	NP_057425.3
PLCE1-AS1	NR_033969.1 linkuse as main transcript	n.231-489T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8 linkuse as main transcript	c.4917+64A>G		intron_variant		1	NM_016341.4	ENSP00000360431	P1	Q9P212-1
PLCE1-AS1	ENST00000425267.8 linkuse as main transcript	n.208-489T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50539

AN:

151986

Hom.:

8682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.471

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.344

GnomAD4 exome

AF:

0.302

AC:

429660

AN:

1420704

Hom.:

66648

AF XY:

0.304

AC XY:

214929

AN XY:

707490

show subpopulations

Gnomad4 AFR exome

AF:

0.435

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.434

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.268

Gnomad4 FIN exome

AF:

0.226

Gnomad4 NFE exome

AF:

0.307

Gnomad4 OTH exome

AF:

0.321

GnomAD4 genome

AF:

0.333

AC:

50592

AN:

152104

Hom.:

8702

Cov.:

AF XY:

0.325

AC XY:

24182

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.261

Gnomad4 ASJ

AF:

0.450

Gnomad4 EAS

AF:

0.229

Gnomad4 SAS

AF:

0.264

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.343

Alfa

AF:

0.269

Hom.:

1159

Bravo

AF:

0.338

Asia WGS

AF:

0.287

AC:

997

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 21. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.4

DANN

Benign

0.70

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