chr10-94030532-TA-T

Position:

• chr10-94030532-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016341.4(PLCE1):​c.-364-141del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 147,502 control chromosomes in the GnomAD database, including 126 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.021 (126 hom., cov: 32)
• Consequence: PLCE1 NM_016341.4 intron
• Clinical Significance: 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-TA-T is Benign according to our data. Variant chr10-94030532-TA-T is described in ClinVar as [Benign]. Clinvar id is 1260323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCE1	NM_016341.4	c.-364-141del		intron_variant		ENST00000371380.8	NP_057425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCE1	ENST00000371380.8	c.-364-141del		intron_variant		1	NM_016341.4	ENSP00000360431	P1
PLCE1	ENST00000692396.1	c.-364-141del		intron_variant				ENSP00000508605
PLCE1	ENST00000675487.1	c.-364-141del		intron_variant, NMD_transcript_variant				ENSP00000502340

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3155 AN: 147416 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.000587

Gnomad EAS AF: 0.000592

Gnomad SAS AF: 0.000641

Gnomad FIN AF: 0.000527

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000466

Gnomad OTH AF: 0.0198

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

GnomAD4 genome AF: 0.0214 AC: 3163 AN: 147502 Hom.: 126 Cov.: 32 AF XY: 0.0212 AC XY: 1524 AN XY: 71780

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.000587

Gnomad4 EAS AF: 0.000594

Gnomad4 SAS AF: 0.000643

Gnomad4 FIN AF: 0.000527

Gnomad4 NFE AF: 0.000466

Gnomad4 OTH AF: 0.0196

Alfa AF: 0.000500 Hom.: 0

Bravo AF: 0.0250

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 07, 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;