chr1-152686964-T-G

Variant names:

• chr1-152686964-T-G
• rs755570329
• NM_014357.5:c.121T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014357.5(LCE2B):​c.121T>G​(p.Ser41Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S41F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: LCE2B NM_014357.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.884
• Publications: 0 publications found

Genes affected

LCE2B (HGNC:16610): (late cornified envelope 2B) This gene is one of the at least 20 genes expressed during epidermal differentiation and located on chromosomal band 1q21. This gene is involved in epidermal differentiation, and it is expressed at high levels in normal and psoriatic skin, but not in cultured keratinocytes or in any other tested cell types or tissues. [provided by RefSeq, Jul 2008]

ENSG00000304363 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04328382).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014357.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE2B	NM_014357.5	MANE Select	c.121T>G	p.Ser41Ala	missense	Exon 2 of 2	NP_055172.1	O14633

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCE2B	ENST00000368780.4	TSL:1 MANE Select	c.121T>G	p.Ser41Ala	missense	Exon 2 of 2	ENSP00000357769.3	O14633
	ENSG00000304363	ENST00000802896.1		n.81-8447A>C		intron	N/A
	ENSG00000304363	ENST00000802897.1		n.69-20238A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251370 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461608 Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33310

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.23
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.88
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.088
Sift	Uncertain	0.023	D
Sift4G	Benign	0.78	T
Polyphen		0.0020	B
Vest4		0.14
MutPred		0.072		Loss of glycosylation at S41 (P = 0.0147)
MVP		0.040
MPC		0.0031
ClinPred		0.026	T
GERP RS		1.2
Varity_R		0.059
gMVP		0.015
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs755570329; hg19: chr1-152659440;