8-42329636-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001556.3(IKBKB):c.2205+422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 984,660 control chromosomes in the GnomAD database, including 400,789 homozygotes. 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 0.76 (48261 hom., cov: 32)
  • Exomes 𝑓: 0.92 (352528 hom.)
• Consequence: IKBKB NM_001556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKB	NM_001556.3	c.2205+422A>G		intron_variant		ENST00000520810.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKBKB	ENST00000520810.6	c.2205+422A>G		intron_variant		1	NM_001556.3	P1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115932 AN: 152056 Hom.: 48243 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.804

GnomAD4 exome AF: 0.916 AC: 762942 AN: 832486 Hom.: 352528 Cov.: 25 AF XY: 0.917 AC XY: 352506 AN XY: 384442

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.916

Gnomad4 ASJ exome AF: 0.935

Gnomad4 EAS exome AF: 0.859

Gnomad4 SAS exome AF: 0.779

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.932

Gnomad4 OTH exome AF: 0.887

GnomAD4 genome AF: 0.762 AC: 115978 AN: 152174 Hom.: 48261 Cov.: 32 AF XY: 0.760 AC XY: 56539 AN XY: 74380

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.803

Alfa AF: 0.900 Hom.: 63039

Bravo AF: 0.755

Asia WGS AF: 0.730 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.50
Dann	Benign	0.34

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: rs6474388; hg19: chr8-42187154;