rs11986055

Positions:

• chr8-42277660-A-C
• chr8-42277660-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.105+5455A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,762 control chromosomes in the GnomAD database, including 7,923 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 0.21 (7923 hom., cov: 31)
• Consequence: IKBKB NM_001556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKB	NM_001556.3	c.105+5455A>C		intron_variant		ENST00000520810.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKBKB	ENST00000520810.6	c.105+5455A>C		intron_variant		1	NM_001556.3	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32165 AN: 151644 Hom.: 7891 Cov.: 31

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.212 AC: 32245 AN: 151762 Hom.: 7923 Cov.: 31 AF XY: 0.214 AC XY: 15835 AN XY: 74152

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.0972

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0363

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0505 Hom.: 1246

Bravo AF: 0.224

Asia WGS AF: 0.261 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.91
DANN	Benign	0.48

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: rs11986055; hg19: chr8-42135178;