Variant 8-42271424-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001556.3(IKBKB):c.-64C>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 0.0186 in 1,392,528 control chromosomes in the GnomAD database, including 664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 145 hom., cov: 32)

Exomes 𝑓: 0.018 ( 519 hom. )

Consequence

IKBKB
NM_001556.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.670

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 8-42271424-C-T is Benign according to our data. Variant chr8-42271424-C-T is described in ClinVar as [Benign]. Clinvar id is 1245244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKB	NM_001556.3 linkuse as main transcript	c.-64C>T		5_prime_UTR_variant	1/22	ENST00000520810.6	NP_001547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKBKB	ENST00000520810.6 linkuse as main transcript	c.-64C>T		5_prime_UTR_variant	1/22	1	NM_001556.3	ENSP00000430684	P1	O14920-1

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3209

AN:

150776

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00582

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0145

Gnomad EAS

AF:

0.000598

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0149

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.0159

GnomAD3 exomes

AF:

0.0380

AC:

4782

AN:

125808

Hom.:

276

AF XY:

0.0318

AC XY:

2199

AN XY:

69148

show subpopulations

Gnomad AFR exome

AF:

0.00335

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.000101

Gnomad SAS exome

AF:

0.0148

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0303

GnomAD4 exome

AF:

0.0183

AC:

22689

AN:

1241638

Hom.:

519

Cov.:

AF XY:

0.0179

AC XY:

11045

AN XY:

616442

show subpopulations

Gnomad4 AFR exome

AF:

0.00345

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.0000908

Gnomad4 SAS exome

AF:

0.0152

Gnomad4 FIN exome

AF:

0.0170

Gnomad4 NFE exome

AF:

0.0156

Gnomad4 OTH exome

AF:

0.0154

GnomAD4 genome

AF:

0.0214

AC:

3223

AN:

150890

Hom.:

145

Cov.:

AF XY:

0.0234

AC XY:

1726

AN XY:

73770

show subpopulations

Gnomad4 AFR

AF:

0.00581

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.0145

Gnomad4 EAS

AF:

0.000599

Gnomad4 SAS

AF:

0.0130

Gnomad4 FIN

AF:

0.0149

Gnomad4 NFE

AF:

0.0154

Gnomad4 OTH

AF:

0.0157

Alfa

AF:

0.0203

Hom.:

Bravo

AF:

0.0248

Asia WGS

AF:

0.00809

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over