Variant 10-94089340-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001165979.2(PLCE1):c.246G>A(p.Lys82Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00776 in 1,611,550 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 61 hom. )

Consequence

PLCE1
NM_001165979.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.426

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-AS2 (HGNC:51206): (PLCE1 antisense RNA 2)

PLCE1-AS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 10-94089340-G-A is Benign according to our data. Variant chr10-94089340-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1182170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.426 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00938 (1429/152292) while in subpopulation AFR AF= 0.0141 (585/41568). AF 95% confidence interval is 0.0131. There are 14 homozygotes in gnomad4. There are 665 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4 link	c.1207-42834G>A		intron_variant		ENST00000371380.8	NP_057425.3	Q9P212-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8 link	c.1207-42834G>A		intron_variant		1	NM_016341.4	ENSP00000360431.2		Q9P212-1

Frequencies

GnomAD3 genomes

AF:

0.00935

AC:

1423

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00775

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00700

AC:

1731

AN:

247190

Hom.:

AF XY:

0.00733

AC XY:

984

AN XY:

134324

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.00582

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00724

Gnomad FIN exome

AF:

0.000700

Gnomad NFE exome

AF:

0.00826

Gnomad OTH exome

AF:

0.00949

GnomAD4 exome

AF:

0.00759

AC:

11080

AN:

1459258

Hom.:

Cov.:

AF XY:

0.00775

AC XY:

5620

AN XY:

725546

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.00590

Gnomad4 ASJ exome

AF:

0.0141

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00730

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00769

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00938

AC:

1429

AN:

152292

Hom.:

Cov.:

AF XY:

0.00893

AC XY:

665

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00775

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00869

Hom.:

Bravo

AF:

0.00998

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0113

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 20, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.78

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