chr10-94284977-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016341.4(PLCE1):​c.5035+12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,389,412 control chromosomes in the GnomAD database, including 95,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8085 hom., cov: 32)
Exomes 𝑓: 0.37 ( 87196 hom. )

Consequence

PLCE1
NM_016341.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.14

Publications

9 publications found
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-AS1 (HGNC:45193): (PLCE1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 10-94284977-C-A is Benign according to our data. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-94284977-C-A is described in CliVar as Benign. Clinvar id is 260722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLCE1NM_016341.4 linkc.5035+12C>A intron_variant Intron 22 of 32 ENST00000371380.8 NP_057425.3 Q9P212-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLCE1ENST00000371380.8 linkc.5035+12C>A intron_variant Intron 22 of 32 1 NM_016341.4 ENSP00000360431.2 Q9P212-1

Frequencies

GnomAD3 genomes
AF:
0.289
AC:
43924
AN:
151882
Hom.:
8073
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0707
Gnomad AMI
AF:
0.320
Gnomad AMR
AF:
0.431
Gnomad ASJ
AF:
0.263
Gnomad EAS
AF:
0.182
Gnomad SAS
AF:
0.259
Gnomad FIN
AF:
0.495
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.371
Gnomad OTH
AF:
0.282
GnomAD2 exomes
AF:
0.353
AC:
87480
AN:
247582
AF XY:
0.348
show subpopulations
Gnomad AFR exome
AF:
0.0634
Gnomad AMR exome
AF:
0.526
Gnomad ASJ exome
AF:
0.279
Gnomad EAS exome
AF:
0.175
Gnomad FIN exome
AF:
0.490
Gnomad NFE exome
AF:
0.374
Gnomad OTH exome
AF:
0.340
GnomAD4 exome
AF:
0.368
AC:
455205
AN:
1237412
Hom.:
87196
Cov.:
18
AF XY:
0.363
AC XY:
228023
AN XY:
627404
show subpopulations
African (AFR)
AF:
0.0592
AC:
1690
AN:
28554
American (AMR)
AF:
0.518
AC:
22957
AN:
44346
Ashkenazi Jewish (ASJ)
AF:
0.281
AC:
6924
AN:
24652
East Asian (EAS)
AF:
0.206
AC:
7935
AN:
38516
South Asian (SAS)
AF:
0.275
AC:
22436
AN:
81470
European-Finnish (FIN)
AF:
0.491
AC:
26151
AN:
53244
Middle Eastern (MID)
AF:
0.219
AC:
1144
AN:
5228
European-Non Finnish (NFE)
AF:
0.383
AC:
348156
AN:
908600
Other (OTH)
AF:
0.337
AC:
17812
AN:
52802
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
13031
26062
39094
52125
65156
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
9998
19996
29994
39992
49990
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.289
AC:
43948
AN:
152000
Hom.:
8085
Cov.:
32
AF XY:
0.295
AC XY:
21910
AN XY:
74288
show subpopulations
African (AFR)
AF:
0.0705
AC:
2926
AN:
41498
American (AMR)
AF:
0.432
AC:
6591
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.263
AC:
910
AN:
3466
East Asian (EAS)
AF:
0.182
AC:
943
AN:
5172
South Asian (SAS)
AF:
0.259
AC:
1246
AN:
4804
European-Finnish (FIN)
AF:
0.495
AC:
5217
AN:
10532
Middle Eastern (MID)
AF:
0.173
AC:
51
AN:
294
European-Non Finnish (NFE)
AF:
0.371
AC:
25180
AN:
67954
Other (OTH)
AF:
0.281
AC:
593
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1450
2899
4349
5798
7248
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
434
868
1302
1736
2170
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.334
Hom.:
20601
Bravo
AF:
0.276
Asia WGS
AF:
0.197
AC:
682
AN:
3474

ClinVar

Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Nephrotic syndrome, type 3 Benign:4
-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Oct 25, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Oct 09, 2014
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

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. -

not specified Benign:3
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

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 63% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 59. Only high quality variants are reported. -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

not provided Benign:3
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
10
DANN
Benign
0.61
PhyloP100
1.1
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

Publications

Other links and lift over

dbSNP: rs3736901; hg19: chr10-96044734; COSMIC: COSV53343096; API