1-152805268-C-G

Variant names:

• chr1-152805268-C-G
• rs150691692
• NM_178351.4:c.211G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178351.4(LCE1C):​c.211G>C​(p.Gly71Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000405 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00042 (0 hom.)
• Consequence: LCE1C NM_178351.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 0 publications found

Genes affected

LCE1C (HGNC:29464): (late cornified envelope 1C) Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.054454595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCE1C	NM_178351.4	c.211G>C	p.Gly71Arg	missense_variant	Exon 2 of 2	ENST00000607093.2	NP_848128.1
LCE1C	NM_001276331.2	c.121G>C	p.Gly41Arg	missense_variant	Exon 3 of 3		NP_001263260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCE1C	ENST00000607093.2	c.211G>C	p.Gly71Arg	missense_variant	Exon 2 of 2	6	NM_178351.4	ENSP00000475270.1
LCE1C	ENST00000606576.1	c.121G>C	p.Gly41Arg	missense_variant	Exon 3 of 3	3		ENSP00000476034.1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152136 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000192 AC: 48 AN: 250590 AF XY: 0.000140

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000417 AC: 610 AN: 1461736 Hom.: 0 Cov.: 33 AF XY: 0.000406 AC XY: 295 AN XY: 727160

African (AFR) AF: 0.000179 AC: 6 AN: 33474

American (AMR) AF: 0.000224 AC: 10 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.000515 AC: 573 AN: 1111984

Other (OTH) AF: 0.000282 AC: 17 AN: 60382

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152254 Hom.: 0 Cov.: 31 AF XY: 0.000255 AC XY: 19 AN XY: 74454

African (AFR) AF: 0.000120 AC: 5 AN: 41548

American (AMR) AF: 0.000523 AC: 8 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000313 Hom.: 0

Bravo AF: 0.000261

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.211G>C (p.G71R) alteration is located in exon 2 (coding exon 1) of the LCE1C gene. This alteration results from a G to C substitution at nucleotide position 211, causing the glycine (G) at amino acid position 71 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.037	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.49	T;.
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		2.2
Sift4G	Uncertain	0.017	D;.
Polyphen		1.0	D;.
Vest4		0.30
MutPred		0.21		Gain of MoRF binding (P = 0.0087);.;
MVP		0.35
ClinPred		0.16	T
GERP RS		3.4
Varity_R		0.73
gMVP		0.016
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs150691692; hg19: chr1-152777744;