rs11187877

Positions:

• chr10-94332364-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016341.4(PLCE1):​c.*4421G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 152,218 control chromosomes in the GnomAD database, including 483 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 0.072 (483 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLCE1 NM_016341.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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]

NOC3L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.*4421G>A		3_prime_UTR_variant	33/33	ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.*4421G>A		3_prime_UTR_variant	33/33	1	NM_016341.4	ENSP00000360431.2

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10939 AN: 152100 Hom.: 483 Cov.: 31

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0768

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.0920

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0719 AC: 10952 AN: 152218 Hom.: 483 Cov.: 31 AF XY: 0.0686 AC XY: 5105 AN XY: 74428

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.0767

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.0446

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.0860

Gnomad4 OTH AF: 0.0911

Alfa AF: 0.0805 Hom.: 129

Bravo AF: 0.0752

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.1
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11187877; hg19: chr10-96092121;