10-94310618-A-G

Variant names:

• chr10-94310618-A-G
• rs3781264
• NM_016341.4:c.6003+1919A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016341.4(PLCE1):​c.6003+1919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,038 control chromosomes in the GnomAD database, including 4,873 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (4873 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 46 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: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016341.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	NM_016341.4	MANE Select	c.6003+1919A>G		intron	N/A	NP_057425.3
	PLCE1	NM_001288989.2		c.5955+1919A>G		intron	N/A	NP_001275918.1	B7ZM61
	PLCE1	NM_001165979.2		c.5079+1919A>G		intron	N/A	NP_001159451.1	Q9P212-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCE1	ENST00000371380.8	TSL:1 MANE Select	c.6003+1919A>G		intron	N/A	ENSP00000360431.2	Q9P212-1
	PLCE1	ENST00000371375.2	TSL:1	c.5079+1919A>G		intron	N/A	ENSP00000360426.1	Q9P212-2
	PLCE1	ENST00000875452.1		c.6003+1919A>G		intron	N/A	ENSP00000545511.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38051 AN: 151920 Hom.: 4873 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.250 AC: 38062 AN: 152038 Hom.: 4873 Cov.: 32 AF XY: 0.246 AC XY: 18243 AN XY: 74308

African (AFR) AF: 0.213 AC: 8831 AN: 41476

American (AMR) AF: 0.213 AC: 3252 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1455 AN: 3466

East Asian (EAS) AF: 0.191 AC: 988 AN: 5166

South Asian (SAS) AF: 0.221 AC: 1063 AN: 4818

European-Finnish (FIN) AF: 0.201 AC: 2126 AN: 10594

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19369 AN: 67948

Other (OTH) AF: 0.269 AC: 567 AN: 2108

Alfa AF: 0.276 Hom.: 22451

Bravo AF: 0.247

Asia WGS AF: 0.220 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.69
PhyloP100		-0.30
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: rs3781264; hg19: chr10-96070375; COSMIC: COSV53339397;