Variant 8-42271381-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001556.3(IKBKB):c.-107G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,510,110 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

IKBKB
NM_001556.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.201

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046812594).

BP6

Variant 8-42271381-G-C is Benign according to our data. Variant chr8-42271381-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3039446.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-42271381-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000913 (139/152306) while in subpopulation SAS AF= 0.0029 (14/4830). AF 95% confidence interval is 0.00175. There are 0 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKB	NM_001556.3 linkuse as main transcript	c.-107G>C		5_prime_UTR_variant	1/22	ENST00000520810.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKBKB	ENST00000520810.6 linkuse as main transcript	c.-107G>C		5_prime_UTR_variant	1/22	1	NM_001556.3	P1	O14920-1

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

140

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00129

AC:

169

AN:

131282

Hom.:

AF XY:

0.00147

AC XY:

106

AN XY:

71942

show subpopulations

Gnomad AFR exome

AF:

0.000676

Gnomad AMR exome

AF:

0.0000823

Gnomad ASJ exome

AF:

0.00222

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00308

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00140

Gnomad OTH exome

AF:

0.000989

GnomAD4 exome

AF:

0.00127

AC:

1718

AN:

1357804

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

902

AN XY:

671412

show subpopulations

Gnomad4 AFR exome

AF:

0.000452

Gnomad4 AMR exome

AF:

0.0000843

Gnomad4 ASJ exome

AF:

0.00244

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.000359

Gnomad4 NFE exome

AF:

0.00119

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.000913

AC:

139

AN:

152306

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.000793

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.00147

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

IKBKB-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 30, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.1

DANN

Benign

0.68

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N

PROVEAN

Benign

0.060

REVEL

Benign

0.071

Sift

Benign

0.85

Polyphen

0.0010

Vest4

0.083

MVP

0.35

ClinPred

0.0015

GERP RS

-0.29

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