rs151057347
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_001556.3(IKBKB):c.1702A>C(p.Arg568=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00239 in 1,610,070 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 10 hom. )
Consequence
IKBKB
NM_001556.3 synonymous
NM_001556.3 synonymous
Scores
1
1
6
Clinical Significance
Conservation
PhyloP100: 5.66
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008109927).
BP6
?
Variant 8-42321909-A-C is Benign according to our data. Variant chr8-42321909-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 474792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-42321909-A-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00185 (282/152318) while in subpopulation NFE AF= 0.00306 (208/68034). AF 95% confidence interval is 0.00272. There are 1 homozygotes in gnomad4. There are 118 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.1702A>C | p.Arg568= | synonymous_variant | 17/22 | ENST00000520810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IKBKB | ENST00000520810.6 | c.1702A>C | p.Arg568= | synonymous_variant | 17/22 | 1 | NM_001556.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00186 AC: 283AN: 152200Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00172 AC: 427AN: 247740Hom.: 1 AF XY: 0.00168 AC XY: 225AN XY: 134032
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GnomAD4 exome AF: 0.00244 AC: 3559AN: 1457752Hom.: 10 Cov.: 30 AF XY: 0.00246 AC XY: 1786AN XY: 725362
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GnomAD4 genome ? AF: 0.00185 AC: 282AN: 152318Hom.: 1 Cov.: 32 AF XY: 0.00158 AC XY: 118AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | IKBKB: BP4 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
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_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationTaster
Benign
D;D;D;D;D
Vest4
MVP
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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