rs2077218

Variant names:

• chr10-94311804-G-A
• rs2077218
• NM_016341.4:c.6004-1450G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-94311804-G-A
• chr10-94311804-G-C

Variant summary

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

The NM_016341.4(PLCE1):​c.6004-1450G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,076 control chromosomes in the GnomAD database, including 50,401 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 0.81 (50401 hom., cov: 31)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.6004-1450G>A		intron_variant	Intron 27 of 32	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.6004-1450G>A		intron_variant	Intron 27 of 32	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123444 AN: 151958 Hom.: 50338 Cov.: 31

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.813 AC: 123565 AN: 152076 Hom.: 50401 Cov.: 31 AF XY: 0.814 AC XY: 60507 AN XY: 74350

African (AFR) AF: 0.883 AC: 36619 AN: 41472

American (AMR) AF: 0.809 AC: 12346 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2840 AN: 3472

East Asian (EAS) AF: 0.707 AC: 3653 AN: 5166

South Asian (SAS) AF: 0.826 AC: 3982 AN: 4818

European-Finnish (FIN) AF: 0.839 AC: 8876 AN: 10576

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52621 AN: 67988

Other (OTH) AF: 0.790 AC: 1668 AN: 2112

Alfa AF: 0.785 Hom.: 140338

Bravo AF: 0.808

Asia WGS AF: 0.796 AC: 2766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		0.059
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: rs2077218; hg19: chr10-96071561;