rs41268500

Positions:

• chr1-152798137-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4 BA1

The NM_178352.3(LCE1D):​c.343T>G​(p.Ter115Glyext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,374,926 control chromosomes in the GnomAD database, including 4,991 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 0.057 (341 hom., cov: 22)
  • Exomes 𝑓: 0.050 (4650 hom.)
• Consequence: LCE1D NM_178352.3 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830

Genes affected

LCE1D (HGNC:29465): (late cornified envelope 1D) Enables identical protein binding activity. Involved in cognition. Acts upstream of or within cellular response to calcium ion. Located in cornified envelope and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM4: Stoplost variant in NM_178352.3 Downstream stopcodon found after 138 codons.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCE1D	NM_178352.3	c.343T>G	p.Ter115Glyext*?	stop_lost	2/2	ENST00000326233.7	NP_848129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCE1D	ENST00000326233.7	c.343T>G	p.Ter115Glyext*?	stop_lost	2/2	5	NM_178352.3	ENSP00000316737.6

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 7678 AN: 135574 Hom.: 340 Cov.: 22

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.0687

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.0798

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.0438

Gnomad NFE AF: 0.0424

Gnomad OTH AF: 0.0538

GnomAD3 exomes AF: 0.0509 AC: 9126 AN: 179442 Hom.: 612 AF XY: 0.0529 AC XY: 5113 AN XY: 96668

Gnomad AFR exome AF: 0.0891

Gnomad AMR exome AF: 0.0273

Gnomad ASJ exome AF: 0.0520

Gnomad EAS exome AF: 0.0360

Gnomad SAS exome AF: 0.0981

Gnomad FIN exome AF: 0.0439

Gnomad NFE exome AF: 0.0444

Gnomad OTH exome AF: 0.0546

GnomAD4 exome AF: 0.0497 AC: 61638 AN: 1239246 Hom.: 4650 Cov.: 30 AF XY: 0.0510 AC XY: 31227 AN XY: 611998

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.0288

Gnomad4 ASJ exome AF: 0.0482

Gnomad4 EAS exome AF: 0.0331

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.0461

Gnomad4 NFE exome AF: 0.0462

Gnomad4 OTH exome AF: 0.0599

GnomAD4 genome AF: 0.0567 AC: 7688 AN: 135680 Hom.: 341 Cov.: 22 AF XY: 0.0566 AC XY: 3764 AN XY: 66464

Gnomad4 AFR AF: 0.0875

Gnomad4 AMR AF: 0.0454

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.0383

Gnomad4 SAS AF: 0.0792

Gnomad4 FIN AF: 0.0416

Gnomad4 NFE AF: 0.0424

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.0393 Hom.: 59

TwinsUK AF: 0.0413 AC: 153

ALSPAC AF: 0.0431 AC: 166

ESP6500AA AF: 0.0673 AC: 271

ESP6500EA AF: 0.0356 AC: 266

ExAC AF: 0.0443 AC: 5023

Asia WGS AF: 0.0680 AC: 238 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.9
DANN	Benign	0.56
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.36	N
Vest4		0.0070
GERP RS		2.4

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: rs41268500; hg19: chr1-152770613; COSMIC: COSV58270512;