NM_001174096.2:c.59-45043T>A

Variant summary

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

The NM_001174096.2(ZEB1):​c.59-45043T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,000 control chromosomes in the GnomAD database, including 14,187 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 0.28 ( 14187 hom., cov: 32)

Consequence

ZEB1
NM_001174096.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610

Publications

1 publications found
Variant links:
Genes affected
ZEB1 (HGNC:11642): (zinc finger E-box binding homeobox 1) This gene encodes a zinc finger transcription factor. The encoded protein likely plays a role in transcriptional repression of interleukin 2. Mutations in this gene have been associated with posterior polymorphous corneal dystrophy-3 and late-onset Fuchs endothelial corneal dystrophy. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2010]
ZEB1 Gene-Disease associations (from GenCC):
  • posterior polymorphous corneal dystrophy 3
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • Fuchs' endothelial dystrophy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • posterior polymorphous corneal dystrophy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • corneal dystrophy, Fuchs endothelial, 6
    Inheritance: AD Classification: LIMITED Submitted by: G2P

Genome browser will be placed here

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=-0.79).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZEB1NM_001174096.2 linkc.59-45043T>A intron_variant Intron 1 of 8 ENST00000424869.6 NP_001167567.1 P37275-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZEB1ENST00000424869.6 linkc.59-45043T>A intron_variant Intron 1 of 8 5 NM_001174096.2 ENSP00000415961.2 P37275-2F6TDF5

Frequencies

GnomAD3 genomes
AF:
0.283
AC:
42933
AN:
151880
Hom.:
14129
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.804
Gnomad AMI
AF:
0.0110
Gnomad AMR
AF:
0.140
Gnomad ASJ
AF:
0.149
Gnomad EAS
AF:
0.206
Gnomad SAS
AF:
0.163
Gnomad FIN
AF:
0.0721
Gnomad MID
AF:
0.187
Gnomad NFE
AF:
0.0571
Gnomad OTH
AF:
0.233
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.283
AC:
43036
AN:
152000
Hom.:
14187
Cov.:
32
AF XY:
0.278
AC XY:
20689
AN XY:
74312
show subpopulations
African (AFR)
AF:
0.804
AC:
33355
AN:
41470
American (AMR)
AF:
0.140
AC:
2131
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.149
AC:
515
AN:
3468
East Asian (EAS)
AF:
0.206
AC:
1068
AN:
5174
South Asian (SAS)
AF:
0.162
AC:
779
AN:
4818
European-Finnish (FIN)
AF:
0.0721
AC:
764
AN:
10598
Middle Eastern (MID)
AF:
0.190
AC:
56
AN:
294
European-Non Finnish (NFE)
AF:
0.0571
AC:
3874
AN:
67892
Other (OTH)
AF:
0.229
AC:
484
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
743
1486
2229
2972
3715
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
332
664
996
1328
1660
<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:
0.190
Hom.:
1024
Bravo
AF:
0.313
Asia WGS
AF:
0.196
AC:
678
AN:
3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
1.7
DANN
Benign
0.66
PhyloP100
-0.061
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs161255; hg19: chr10-31704923; API