rs13278372

Positions:

• chr8-42324723-A-C
• chr8-42324723-A-T

Variant summary

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

The NM_001556.3(IKBKB):​c.1987-1247A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,758 control chromosomes in the GnomAD database, including 43,349 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 0.71 (43157 hom., cov: 33)
  • Exomes 𝑓: 0.86 (192 hom.)
• Consequence: IKBKB NM_001556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKB	NM_001556.3	c.1987-1247A>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.1987-1247A>C		intron_variant		1	NM_001556.3	ENSP00000430684	P1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107377 AN: 152132 Hom.: 43147 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.763

GnomAD4 exome AF: 0.856 AC: 435 AN: 508 Hom.: 192 Cov.: 0 AF XY: 0.853 AC XY: 331 AN XY: 388

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.958

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.864

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.705 AC: 107399 AN: 152250 Hom.: 43157 Cov.: 33 AF XY: 0.706 AC XY: 52578 AN XY: 74442

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.762

Alfa AF: 0.809 Hom.: 12812

Bravo AF: 0.695

Asia WGS AF: 0.703 AC: 2443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.6
DANN	Benign	0.76

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: rs13278372; hg19: chr8-42182241;