Genetic Variant IKBKB:c.-107G>T (chr8-42271381-G-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001556.3(IKBKB):c.-107G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000442 in 1,357,868 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: 0.0000044 ( 0 hom. )

Consequence

IKBKB
NM_001556.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.201

Publications

5 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38260856).

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.-107G>T	5_prime_UTR	Exon 1 of 22	NP_001547.1	O14920-1
IKBKB	NM_001242778.2		c.-189G>T	5_prime_UTR	Exon 1 of 21	NP_001229707.1	O14920-4
IKBKB	NM_001190720.3		c.-176G>T	5_prime_UTR	Exon 1 of 21	NP_001177649.2	A0A499FJS7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IKBKB	ENST00000520810.6	TSL:1 MANE Select	c.-107G>T	5_prime_UTR	Exon 1 of 22	ENSP00000430684.1	O14920-1
IKBKB	ENST00000519735.5	TSL:1	n.64G>T	non_coding_transcript_exon	Exon 1 of 9
IKBKB	ENST00000957021.1		c.-107G>T	5_prime_UTR	Exon 1 of 22	ENSP00000627080.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000152

AC:

AN:

131282

AF XY:

0.0000139

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000442

AC:

AN:

1357868

Hom.:

Cov.:

AF XY:

0.00000298

AC XY:

AN XY:

671440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30962

American (AMR)

AF:

0.00

AC:

AN:

35608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24996

East Asian (EAS)

AF:

0.0000563

AC:

AN:

35520

South Asian (SAS)

AF:

0.0000381

AC:

AN:

78742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5362

European-Non Finnish (NFE)

AF:

9.47e-7

AC:

AN:

1056346

Other (OTH)

AF:

0.00

AC:

AN:

56886

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.4

(source)

DANN

Benign

0.71

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.34

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.96

PhyloP100

0.20

PROVEAN

Benign

-0.24

REVEL

Benign

0.18

Sift

Benign

0.34

Polyphen

0.14

Vest4

0.12

MutPred

0.80

Gain of sheet (P = 0.0061)

MVP

0.37

ClinPred

0.083

GERP RS

-0.29

PromoterAI

-0.059

Neutral

(source)

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

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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