Genetic Variant IKBKB:c.-24C>T (chr8-42271464-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001556.3(IKBKB):c.-24C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 1,151,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

IKBKB
NM_001556.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.116

Publications

0 publications found

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]

IKBKB links:

IKBKB-DT (HGNC:55254): (IKBKB divergent transcript)

IKBKB-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.200395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001556.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IKBKB	NM_001556.3	MANE Select	c.-24C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	NP_001547.1	O14920-1
IKBKB	NM_001556.3	MANE Select	c.-24C>T	5_prime_UTR	Exon 1 of 22	NP_001547.1	O14920-1
IKBKB	NM_001242778.2		c.-106C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	NP_001229707.1	O14920-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IKBKB	ENST00000520810.6	TSL:1 MANE Select	c.-24C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	ENSP00000430684.1	O14920-1
IKBKB	ENST00000520810.6	TSL:1 MANE Select	c.-24C>T	5_prime_UTR	Exon 1 of 22	ENSP00000430684.1	O14920-1
IKBKB	ENST00000519735.5	TSL:1	n.147C>T	non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

108842

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000174

AC:

AN:

1151802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

576124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26280

American (AMR)

AF:

0.00

AC:

AN:

34164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22592

East Asian (EAS)

AF:

0.00

AC:

AN:

33470

South Asian (SAS)

AF:

0.00

AC:

AN:

72456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3632

European-Non Finnish (NFE)

AF:

0.00000228

AC:

AN:

876374

Other (OTH)

AF:

0.00

AC:

AN:

49998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.33

PhyloP100

-0.12

Vest4

0.26

GERP RS

1.4

PromoterAI

-0.049

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over