rs115698972
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS1
The NM_001556.3(IKBKB):c.1504G>A(p.Glu502Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000584 in 1,614,174 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0031 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 4 hom. )
Consequence
IKBKB
NM_001556.3 missense
NM_001556.3 missense
Scores
1
3
13
Clinical Significance
Conservation
PhyloP100: 4.58
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, IKBKB
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00725773).
BP6
?
Variant 8-42319409-G-A is Benign according to our data. Variant chr8-42319409-G-A is described in ClinVar as [Benign]. Clinvar id is 541644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00311 (474/152282) while in subpopulation AFR AF= 0.0109 (454/41554). AF 95% confidence interval is 0.0101. There are 0 homozygotes in gnomad4. There are 211 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IKBKB | NM_001556.3 | c.1504G>A | p.Glu502Lys | missense_variant | 14/22 | ENST00000520810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IKBKB | ENST00000520810.6 | c.1504G>A | p.Glu502Lys | missense_variant | 14/22 | 1 | NM_001556.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00312 AC: 474AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000760 AC: 191AN: 251456Hom.: 1 AF XY: 0.000559 AC XY: 76AN XY: 135896
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GnomAD4 exome AF: 0.000321 AC: 469AN: 1461892Hom.: 4 Cov.: 31 AF XY: 0.000278 AC XY: 202AN XY: 727246
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GnomAD4 genome ? AF: 0.00311 AC: 474AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.00283 AC XY: 211AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
IKBKB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 18, 2024 | This variant is classified as 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 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N;.
REVEL
Benign
Sift
Benign
T;T;.;T;.
Sift4G
Benign
T;T;T;T;.
Polyphen
B;.;.;B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at