rs56230731
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001556.3(IKBKB):c.1083G>A(p.Leu361=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0128 in 1,614,106 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0098 ( 4 hom., cov: 32)
Exomes 𝑓: 0.013 ( 181 hom. )
Consequence
IKBKB
NM_001556.3 synonymous
NM_001556.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.06
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 8-42316862-G-A is Benign according to our data. Variant chr8-42316862-G-A is described in ClinVar as [Benign]. Clinvar id is 474788.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00977 (1488/152284) while in subpopulation NFE AF= 0.0169 (1150/68030). AF 95% confidence interval is 0.0161. There are 4 homozygotes in gnomad4. There are 668 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 4 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IKBKB | NM_001556.3 | c.1083G>A | p.Leu361= | synonymous_variant | 11/22 | ENST00000520810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IKBKB | ENST00000520810.6 | c.1083G>A | p.Leu361= | synonymous_variant | 11/22 | 1 | NM_001556.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00978 AC: 1488AN: 152166Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00925 AC: 2323AN: 251040Hom.: 22 AF XY: 0.00885 AC XY: 1201AN XY: 135742
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GnomAD4 exome AF: 0.0131 AC: 19185AN: 1461822Hom.: 181 Cov.: 31 AF XY: 0.0126 AC XY: 9176AN XY: 727214
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GnomAD4 genome ? AF: 0.00977 AC: 1488AN: 152284Hom.: 4 Cov.: 32 AF XY: 0.00897 AC XY: 668AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe combined immunodeficiency due to IKK2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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