8-42316559-G-A

Position:

• chr8-42316559-G-A

Variant summary

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

The NM_001556.3(IKBKB):​c.931-151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 873,876 control chromosomes in the GnomAD database, including 4,559 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 0.12 (1899 hom., cov: 32)
  • Exomes 𝑓: 0.059 (2660 hom.)
• Consequence: IKBKB NM_001556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKB	NM_001556.3	c.931-151G>A		intron_variant		ENST00000520810.6	NP_001547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKBKB	ENST00000520810.6	c.931-151G>A		intron_variant		1	NM_001556.3	ENSP00000430684	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17689 AN: 152088 Hom.: 1897 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0328

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.0594 AC: 42882 AN: 721670 Hom.: 2660 AF XY: 0.0627 AC XY: 23001 AN XY: 366914

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.0461

Gnomad4 ASJ exome AF: 0.0211

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.0939

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0712

GnomAD4 genome AF: 0.116 AC: 17713 AN: 152206 Hom.: 1899 Cov.: 32 AF XY: 0.122 AC XY: 9063 AN XY: 74404

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0328

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0562 Hom.: 296

Bravo AF: 0.115

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.65

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: rs12676482; hg19: chr8-42174077;