8-42298528-A-G

Position:

• chr8-42298528-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.388+5016A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 953,402 control chromosomes in the GnomAD database, including 17,367 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 0.25 (9766 hom., cov: 33)
  • Exomes 𝑓: 0.10 (7601 hom.)
• Consequence: IKBKB NM_001556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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]

LOC105379395 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKB	NM_001556.3	c.388+5016A>G		intron_variant		ENST00000520810.6
LOC105379395	XR_949714.3	n.2643A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKBKB	ENST00000520810.6	c.388+5016A>G		intron_variant		1	NM_001556.3	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38521 AN: 152114 Hom.: 9719 Cov.: 33

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.105 AC: 83822 AN: 801170 Hom.: 7601 Cov.: 13 AF XY: 0.104 AC XY: 38569 AN XY: 370862

Gnomad4 AFR exome AF: 0.708

Gnomad4 AMR exome AF: 0.0907

Gnomad4 ASJ exome AF: 0.0474

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0879

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.254 AC: 38620 AN: 152232 Hom.: 9766 Cov.: 33 AF XY: 0.252 AC XY: 18770 AN XY: 74462

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0794

Gnomad4 OTH AF: 0.206

Alfa AF: 0.125 Hom.: 1255

Bravo AF: 0.268

Asia WGS AF: 0.285 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.41

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: rs9694958; hg19: chr8-42156046;