GeneBe

NM_178351.4:c.-21+519G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178351.4(LCE1C):​c.-21+519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,158 control chromosomes in the GnomAD database, including 2,578 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 0.18 ( 2578 hom., cov: 32)

Consequence

LCE1C
NM_178351.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.894

Publications

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

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LCE1CNM_178351.4 linkc.-21+519G>A intron_variant Intron 1 of 1 ENST00000607093.2 NP_848128.1 Q5T751
LCE1CNM_001276331.2 linkc.-21+519G>A intron_variant Intron 1 of 2 NP_001263260.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LCE1CENST00000607093.2 linkc.-21+519G>A intron_variant Intron 1 of 1 6 NM_178351.4 ENSP00000475270.1 Q5T751
LCE1CENST00000606576.1 linkc.-21+519G>A intron_variant Intron 1 of 2 3 ENSP00000476034.1 U3KQM4

Frequencies

GnomAD3 genomes
AF:
0.176
AC:
26790
AN:
152040
Hom.:
2567
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.249
Gnomad AMI
AF:
0.115
Gnomad AMR
AF:
0.150
Gnomad ASJ
AF:
0.165
Gnomad EAS
AF:
0.118
Gnomad SAS
AF:
0.182
Gnomad FIN
AF:
0.154
Gnomad MID
AF:
0.196
Gnomad NFE
AF:
0.146
Gnomad OTH
AF:
0.185
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.176
AC:
26830
AN:
152158
Hom.:
2578
Cov.:
32
AF XY:
0.176
AC XY:
13059
AN XY:
74396
show subpopulations
African (AFR)
AF:
0.249
AC:
10322
AN:
41476
American (AMR)
AF:
0.150
AC:
2299
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.165
AC:
571
AN:
3468
East Asian (EAS)
AF:
0.118
AC:
613
AN:
5178
South Asian (SAS)
AF:
0.181
AC:
872
AN:
4822
European-Finnish (FIN)
AF:
0.154
AC:
1634
AN:
10592
Middle Eastern (MID)
AF:
0.197
AC:
58
AN:
294
European-Non Finnish (NFE)
AF:
0.146
AC:
9947
AN:
68008
Other (OTH)
AF:
0.193
AC:
409
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1108
2216
3324
4432
5540
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
294
588
882
1176
1470
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.154
Hom.:
4570
Bravo
AF:
0.177
Asia WGS
AF:
0.182
AC:
630
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
8.0
DANN
Benign
0.46
PhyloP100
0.89
Mutation Taster
=100/0
polymorphism (auto)

Splicing

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

Publications

Other links and lift over

dbSNP: rs6701221; hg19: chr1-152778558; API