rs10888501

Variant names:

• chr1-152565478-G-A
• rs10888501
• NM_178435.4:c.*452C>T

Variant summary

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

The NM_178435.4(LCE3E):​c.*452C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,774 control chromosomes in the GnomAD database, including 18,685 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 0.48 (18685 hom., cov: 31)
• Consequence: LCE3E NM_178435.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

Genes affected

LCE3E (HGNC:29463): (late cornified envelope 3E) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE3E	NM_178435.4	c.*452C>T		downstream_gene_variant		ENST00000368789.2	NP_848522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE3E	ENST00000368789.2	c.*452C>T		downstream_gene_variant		1	NM_178435.4	ENSP00000357778.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72127 AN: 151656 Hom.: 18641 Cov.: 31

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.476 AC: 72217 AN: 151774 Hom.: 18685 Cov.: 31 AF XY: 0.483 AC XY: 35823 AN XY: 74168

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.447

Alfa AF: 0.380 Hom.: 20542

Bravo AF: 0.482

Asia WGS AF: 0.530 AC: 1845 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	0.44
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10888501; hg19: chr1-152537954;