rs151057347
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000520810.6(IKBKB):āc.1702A>Cā(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 (ā ā ).
Frequency
Genomes: š 0.0019 ( 1 hom., cov: 32)
Exomes š: 0.0024 ( 10 hom. )
Consequence
IKBKB
ENST00000520810.6 synonymous
ENST00000520810.6 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 -20 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.
BS2
High Homozygotes in GnomAdExome4 at 10 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IKBKB | NM_001556.3 | c.1702A>C | p.Arg568= | synonymous_variant | 17/22 | ENST00000520810.6 | NP_001547.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IKBKB | ENST00000520810.6 | c.1702A>C | p.Arg568= | synonymous_variant | 17/22 | 1 | NM_001556.3 | ENSP00000430684 | 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:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
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, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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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