rs9419788

Variant names:

• chr10-94253948-G-A
• rs9419788
• NM_016341.4:c.3280-242G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016341.4(PLCE1):​c.3280-242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,142 control chromosomes in the GnomAD database, including 35,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (35380 hom., cov: 33)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.264
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-94253948-G-A is Benign according to our data. Variant chr10-94253948-G-A is described in ClinVar as Benign. ClinVar VariationId is 1296564.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.3280-242G>A		intron_variant	Intron 9 of 32	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.3280-242G>A		intron_variant	Intron 9 of 32	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102469 AN: 152024 Hom.: 35352 Cov.: 33

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.682

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.674 AC: 102545 AN: 152142 Hom.: 35380 Cov.: 33 AF XY: 0.670 AC XY: 49809 AN XY: 74360

African (AFR) AF: 0.804 AC: 33365 AN: 41522

American (AMR) AF: 0.553 AC: 8437 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2531 AN: 3466

East Asian (EAS) AF: 0.828 AC: 4288 AN: 5180

South Asian (SAS) AF: 0.743 AC: 3578 AN: 4818

European-Finnish (FIN) AF: 0.508 AC: 5369 AN: 10576

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42685 AN: 67990

Other (OTH) AF: 0.684 AC: 1445 AN: 2114

Alfa AF: 0.653 Hom.: 101430

Bravo AF: 0.681

Asia WGS AF: 0.797 AC: 2773 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.63
PhyloP100		0.26
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

Other links and lift over

dbSNP: rs9419788; hg19: chr10-96013705;