rs149198185

Variant names:

• chr1-152687096-C-T
• rs149198185
• NM_014357.5:c.253C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-152687096-C-T
• chr1-152687096-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014357.5(LCE2B):​c.253C>T​(p.Arg85Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,613,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R85Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: LCE2B NM_014357.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.29
• Publications: 3 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17964083).

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.253C>T	p.Arg85Trp	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.253C>T	p.Arg85Trp	missense	Exon 2 of 2	ENSP00000357769.3	O14633
	ENSG00000304363	ENST00000802896.1		n.81-8579G>A		intron	N/A
	ENSG00000304363	ENST00000802897.1		n.69-20370G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000361 AC: 9 AN: 249390 AF XY: 0.0000222

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: 0.0000709

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 147 AN: 1461716 Hom.: 0 Cov.: 31 AF XY: 0.0000990 AC XY: 72 AN XY: 727172

African (AFR) AF: 0.0000599 AC: 2 AN: 33410

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1111988

Other (OTH) AF: 0.000132 AC: 8 AN: 60392

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152032 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74258

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.000131 AC: 2 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.11
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.2
DANN	Benign	0.65
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-2.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.060
Sift	Uncertain	0.018	D
Sift4G	Benign	0.17	T
Polyphen		0.99	D
Vest4		0.24
MVP		0.25
MPC		0.0028
ClinPred		0.20	T
GERP RS		-4.9
Varity_R		0.046
gMVP		0.042
Mutation Taster		=99/1	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: rs149198185; hg19: chr1-152659572; COSMIC: COSV64227490;