8-42328734-T-C

Position:

• chr8-42328734-T-C

Variant summary

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

The NM_001556.3(IKBKB):​c.2115-390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,168 control chromosomes in the GnomAD database, including 48,247 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 (48247 hom., cov: 32)
• Consequence: IKBKB NM_001556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• 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	Protein	UniProt
IKBKB	NM_001556.3	c.2115-390T>C		intron_variant		ENST00000520810.6	NP_001547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKBKB	ENST00000520810.6	c.2115-390T>C		intron_variant		1	NM_001556.3	ENSP00000430684.1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115915 AN: 152050 Hom.: 48229 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.762 AC: 115960 AN: 152168 Hom.: 48247 Cov.: 32 AF XY: 0.760 AC XY: 56532 AN XY: 74378

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: 0.819

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.804

Alfa AF: 0.788 Hom.: 6021

Bravo AF: 0.754

Asia WGS AF: 0.729 AC: 2532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.53

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: rs6474387; hg19: chr8-42186252;