8-42271448-T-A

Position:

• chr8-42271448-T-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_001556.3(IKBKB):​c.-40T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000071 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IKBKB NM_001556.3 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.436

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 8-42271448-T-A is Benign according to our data. Variant chr8-42271448-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3047209.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKB	NM_001556.3	c.-40T>A		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	c.-40T>A		5_prime_UTR_variant	1/22	1	NM_001556.3	ENSP00000430684.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4 AN: 133266 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000717

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000714 AC: 58 AN: 812404 Hom.: 0 Cov.: 17 AF XY: 0.0000707 AC XY: 29 AN XY: 410304

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000106

Gnomad4 ASJ exome AF: 0.000271

Gnomad4 EAS exome AF: 0.000213

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000136

Gnomad4 NFE exome AF: 0.0000662

Gnomad4 OTH exome AF: 0.000157

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000300 AC: 4 AN: 133336 Hom.: 0 Cov.: 32 AF XY: 0.0000460 AC XY: 3 AN XY: 65184

Gnomad4 AFR AF: 0.0000535

Gnomad4 AMR AF: 0.0000716

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000126

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

IKBKB-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 16, 2024

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_noAF	Benign	-0.77
CADD	Benign	5.3
DANN	Benign	0.78
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

LitVar

Other links and lift over

dbSNP: rs565023239; hg19: chr8-42128966;