10-94030532-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_016341.4(PLCE1):c.-364-141dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 147,574 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0045 (6 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.646

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-94030532-T-TA is Benign according to our data. Variant chr10-94030532-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 1254815.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00449 (662/147574) while in subpopulation SAS AF= 0.0322 (150/4664). AF 95% confidence interval is 0.028. There are 6 homozygotes in gnomad4. There are 350 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCE1	NM_016341.4	c.-364-141dup		intron_variant		ENST00000371380.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCE1	ENST00000371380.8	c.-364-141dup		intron_variant		1	NM_016341.4	P1
PLCE1	ENST00000692396.1	c.-364-141dup		intron_variant
PLCE1	ENST00000675487.1	c.-364-141dup		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 664 AN: 147488 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00115

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000331

Gnomad OTH AF: 0.00149

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

GnomAD4 genome AF: 0.00449 AC: 662 AN: 147574 Hom.: 6 Cov.: 32 AF XY: 0.00487 AC XY: 350 AN XY: 71820

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.00115

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0322

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000331

Gnomad4 OTH AF: 0.00147

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs59044005; hg19: chr10-95790289;