rs140666106
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001556.3(IKBKB):c.1119C>T(p.Asp373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000747 in 1,613,922 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 4 hom. )
Consequence
IKBKB
NM_001556.3 synonymous
NM_001556.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.68
Genes affected
IKBKB (HGNC:5960): (inhibitor of nuclear factor kappa B kinase subunit beta) The protein encoded by this gene phosphorylates the inhibitor in the inhibitor/NF-kappa-B complex, causing dissociation of the inhibitor and activation of NF-kappa-B. The encoded protein itself is found in a complex of proteins. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Sep 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 8-42316898-C-T is Benign according to our data. Variant chr8-42316898-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 474789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-42316898-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.68 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00403 (613/152270) while in subpopulation AFR AF= 0.0142 (591/41540). AF 95% confidence interval is 0.0133. There are 3 homozygotes in gnomad4. There are 279 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IKBKB | NM_001556.3 | c.1119C>T | p.Asp373= | synonymous_variant | 11/22 | ENST00000520810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IKBKB | ENST00000520810.6 | c.1119C>T | p.Asp373= | synonymous_variant | 11/22 | 1 | NM_001556.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00403 AC: 613AN: 152152Hom.: 3 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
613
AN:
152152
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000934 AC: 234AN: 250632Hom.: 2 AF XY: 0.000760 AC XY: 103AN XY: 135526
GnomAD3 exomes
AF:
AC:
234
AN:
250632
Hom.:
AF XY:
AC XY:
103
AN XY:
135526
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000405 AC: 592AN: 1461652Hom.: 4 Cov.: 31 AF XY: 0.000374 AC XY: 272AN XY: 727130
GnomAD4 exome
AF:
AC:
592
AN:
1461652
Hom.:
Cov.:
31
AF XY:
AC XY:
272
AN XY:
727130
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00403 AC: 613AN: 152270Hom.: 3 Cov.: 32 AF XY: 0.00375 AC XY: 279AN XY: 74454
GnomAD4 genome
?
AF:
AC:
613
AN:
152270
Hom.:
Cov.:
32
AF XY:
AC XY:
279
AN XY:
74454
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | IKBKB: BP4, BP7, BS1, BS2 - |
IKBKB-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 10, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Severe combined immunodeficiency due to IKK2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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