14-35404605-C-A
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_020529.3(NFKBIA):c.40G>T(p.Glu14*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NFKBIA
NM_020529.3 stop_gained
NM_020529.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 2.15
Publications
9 publications found
Genes affected
NFKBIA (HGNC:7797): (NFKB inhibitor alpha) This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have been found in ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant disease. [provided by RefSeq, Aug 2011]
NFKBIA Gene-Disease associations (from GenCC):
- ectodermal dysplasia and immunodeficiency 2Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- ectodermal dysplasia and immune deficiencyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-35404605-C-A is Pathogenic according to our data. Variant chr14-35404605-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 14005.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1413996Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 701468
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1413996
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
701468
African (AFR)
AF:
AC:
0
AN:
30534
American (AMR)
AF:
AC:
0
AN:
38650
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25144
East Asian (EAS)
AF:
AC:
0
AN:
35192
South Asian (SAS)
AF:
AC:
0
AN:
80446
European-Finnish (FIN)
AF:
AC:
0
AN:
49830
Middle Eastern (MID)
AF:
AC:
0
AN:
5694
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1089992
Other (OTH)
AF:
AC:
0
AN:
58514
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Ectodermal dysplasia and immunodeficiency 2 Pathogenic:1
Jun 01, 2008
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
PhyloP100
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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