rs201869683

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The ENST00000520810.6(IKBKB):ā€‹c.2228A>Gā€‹(p.Gln743Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q743L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

IKBKB
ENST00000520810.6 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.92
Variant links:
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), IKBKB. . Gene score misZ 2.5876 (greater than the threshold 3.09). Trascript score misZ 3.3125 (greater than threshold 3.09). GenCC has associacion of gene with immunodeficiency 15a, severe combined immunodeficiency due to IKK2 deficiency.
BP4
Computational evidence support a benign effect (MetaRNN=0.10410881).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IKBKBNM_001556.3 linkuse as main transcriptc.2228A>G p.Gln743Arg missense_variant 22/22 ENST00000520810.6 NP_001547.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IKBKBENST00000520810.6 linkuse as main transcriptc.2228A>G p.Gln743Arg missense_variant 22/221 NM_001556.3 ENSP00000430684 P1O14920-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251480
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
18
DANN
Benign
0.83
DEOGEN2
Benign
0.067
T;.;.;T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.12
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.67
.;T;T;T
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-0.59
T
MutationAssessor
Benign
1.6
L;.;.;L
MutationTaster
Benign
0.84
D;D;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.18
N;N;N;.
REVEL
Benign
0.16
Sift
Benign
0.48
T;T;T;.
Sift4G
Benign
0.56
T;T;T;.
Polyphen
0.0
B;.;B;B
Vest4
0.19
MutPred
0.16
Gain of helix (P = 0.0325);.;.;Gain of helix (P = 0.0325);
MVP
0.85
MPC
0.46
ClinPred
0.22
T
GERP RS
5.3
Varity_R
0.15
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201869683; hg19: chr8-42188454; API