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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001556.3(IKBKB):c.-107G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,510,058 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 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:

COSMIC-nc: COSV105222020

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3192578).

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>A	5_prime_UTR	Exon 1 of 22	NP_001547.1	O14920-1
IKBKB	NM_001242778.2		c.-189G>A	5_prime_UTR	Exon 1 of 21	NP_001229707.1	O14920-4
IKBKB	NM_001190720.3		c.-176G>A	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>A	5_prime_UTR	Exon 1 of 22	ENSP00000430684.1	O14920-1
IKBKB	ENST00000519735.5	TSL:1	n.64G>A	non_coding_transcript_exon	Exon 1 of 9
IKBKB	ENST00000957021.1		c.-107G>A	5_prime_UTR	Exon 1 of 22	ENSP00000627080.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000762

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:

0.000247

GnomAD4 exome

AF:

0.00000147

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:

0.0000281

AC:

AN:

35608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24996

East Asian (EAS)

AF:

0.00

AC:

AN:

35520

South Asian (SAS)

AF:

0.00

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:

0.00

AC:

AN:

1056346

Other (OTH)

AF:

0.0000176

AC:

AN:

56886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.4

(source)

DANN

Benign

0.90

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.31

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.99

PhyloP100

0.20

PROVEAN

Benign

0.95

REVEL

Benign

0.18

Sift

Benign

1.0

Polyphen

0.0010

Vest4

0.091

MutPred

0.87

Loss of glycosylation at S3 (P = 0.0309)

MVP

0.27

ClinPred

0.048

GERP RS

-0.29

PromoterAI

-0.042

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over