NM_178435.4:c.-201C>T

Variant names:

• chr1-152566917-G-A
• rs17659389
• NM_178435.4:c.-201C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178435.4(LCE3E):​c.-201C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,122 control chromosomes in the GnomAD database, including 3,170 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 0.18 (3167 hom., cov: 32)
  • Exomes 𝑓: 0.20 (3 hom.)
• Consequence: LCE3E NM_178435.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178435.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE3E	NM_178435.4	MANE Select	c.-201C>T		upstream_gene	N/A	NP_848522.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE3E	ENST00000368789.2	TSL:1 MANE Select	c.-201C>T		upstream_gene	N/A	ENSP00000357778.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27479 AN: 151886 Hom.: 3168 Cov.: 32

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.203 AC: 24 AN: 118 Hom.: 3 AF XY: 0.203 AC XY: 13 AN XY: 64

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 12

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 20 AN: 100

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.181 AC: 27478 AN: 152004 Hom.: 3167 Cov.: 32 AF XY: 0.179 AC XY: 13272 AN XY: 74312

African (AFR) AF: 0.0787 AC: 3266 AN: 41524

American (AMR) AF: 0.133 AC: 2013 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3468

East Asian (EAS) AF: 0.0301 AC: 156 AN: 5180

South Asian (SAS) AF: 0.112 AC: 538 AN: 4820

European-Finnish (FIN) AF: 0.283 AC: 2988 AN: 10572

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17597 AN: 67970

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.217 Hom.: 6999

Bravo AF: 0.163

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		0.20
PromoterAI		-0.056	Neutral

Splicing

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

Other links and lift over

dbSNP: rs17659389; hg19: chr1-152539393;