8-42271464-C-A

Variant names:

• chr8-42271464-C-A
• rs901993530
• NM_001556.3:c.-24C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001556.3(IKBKB):​c.-24C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000868 in 1,151,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: IKBKB NM_001556.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

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-DT (HGNC:55254): (IKBKB divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001556.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKB	NM_001556.3	MANE Select	c.-24C>A		5_prime_UTR	Exon 1 of 22	NP_001547.1	O14920-1
	IKBKB	NM_001242778.2		c.-106C>A		5_prime_UTR	Exon 1 of 21	NP_001229707.1	O14920-4
	IKBKB	NM_001190720.3		c.-93C>A		5_prime_UTR	Exon 1 of 21	NP_001177649.2	A0A499FJS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKB	ENST00000520810.6	TSL:1 MANE Select	c.-24C>A		5_prime_UTR	Exon 1 of 22	ENSP00000430684.1	O14920-1
	IKBKB	ENST00000519735.5	TSL:1	n.147C>A		non_coding_transcript_exon	Exon 1 of 9
	IKBKB	ENST00000957021.1		c.-24C>A		5_prime_UTR	Exon 1 of 22	ENSP00000627080.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.68e-7 AC: 1 AN: 1151800 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 576122

African (AFR) AF: 0.00 AC: 0 AN: 26280

American (AMR) AF: 0.00 AC: 0 AN: 34164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22592

East Asian (EAS) AF: 0.00 AC: 0 AN: 33470

South Asian (SAS) AF: 0.00 AC: 0 AN: 72456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3632

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 876372

Other (OTH) AF: 0.00 AC: 0 AN: 49998

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		-0.12
PromoterAI		-0.0074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs901993530; hg19: chr8-42128982;