1-152686928-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014357.5(LCE2B):​c.85C>T​(p.Pro29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

LCE2B
NM_014357.5 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0220
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.045698702).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LCE2BNM_014357.5 linkuse as main transcriptc.85C>T p.Pro29Ser missense_variant 2/2 ENST00000368780.4 NP_055172.1 O14633

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LCE2BENST00000368780.4 linkuse as main transcriptc.85C>T p.Pro29Ser missense_variant 2/21 NM_014357.5 ENSP00000357769.3 O14633

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152158
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251482
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135916
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000791
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000142
AC:
208
AN:
1461888
Hom.:
0
Cov.:
32
AF XY:
0.000132
AC XY:
96
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000169
Gnomad4 OTH exome
AF:
0.000331
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 17, 2024The c.85C>T (p.P29S) alteration is located in exon 2 (coding exon 1) of the LCE2B gene. This alteration results from a C to T substitution at nucleotide position 85, causing the proline (P) at amino acid position 29 to be replaced by a serine (S). 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
0.092
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
7.7
DANN
Benign
0.32
DEOGEN2
Benign
0.17
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.046
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
2.0
M
PrimateAI
Benign
0.25
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.047
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.074
T
Polyphen
0.015
B
Vest4
0.17
MutPred
0.22
Loss of catalytic residue at P29 (P = 1e-04);
MVP
0.092
MPC
0.0028
ClinPred
0.051
T
GERP RS
0.44
Varity_R
0.057
gMVP
0.044

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs774898505; hg19: chr1-152659404; API