rs1858610

chr10-94280637-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.4795+726G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,072 control chromosomes in the GnomAD database, including 9,076 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 0.34 (9076 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.920

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-AS1 (HGNC:45193): (PLCE1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCE1	NM_016341.4	c.4795+726G>A		intron_variant		ENST00000371380.8
PLCE1-AS1	NR_033969.1	n.331-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCE1	ENST00000371380.8	c.4795+726G>A		intron_variant		1	NM_016341.4	P1
PLCE1-AS1	ENST00000425267.8	n.308-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52143 AN: 151900 Hom.: 9069 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.204 AC: 11 AN: 54 Hom.: 0 Cov.: 0 AF XY: 0.188 AC XY: 6 AN XY: 32

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.208

GnomAD4 genome AF: 0.343 AC: 52169 AN: 152018 Hom.: 9076 Cov.: 32 AF XY: 0.341 AC XY: 25367 AN XY: 74298

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.361

Alfa AF: 0.341 Hom.: 1786

Bravo AF: 0.348

Asia WGS AF: 0.349 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.2
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs1858610; hg19: chr10-96040394;