rs2294100

Variant names:

• chr8-42317785-A-C
• rs2294100
• NM_001556.3:c.1240+14A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-42317785-A-C
• chr8-42317785-A-G
• chr8-42317785-A-T

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.1240+14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,417,142 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: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: IKBKB NM_001556.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 11 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 Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to IKK2 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• immunodeficiency 15a

  Inheritance: AD, AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

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=-0.8).

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.1240+14A>C		intron	N/A	NP_001547.1	O14920-1
	IKBKB	NM_001242778.2		c.1063+14A>C		intron	N/A	NP_001229707.1	O14920-4
	IKBKB	NM_001190720.3		c.1048+14A>C		intron	N/A	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.1240+14A>C		intron	N/A	ENSP00000430684.1	O14920-1
	IKBKB	ENST00000523517.5	TSL:1	n.*59+14A>C		intron	N/A	ENSP00000430114.1	E5RGW5
	IKBKB	ENST00000957021.1		c.1240+14A>C		intron	N/A	ENSP00000627080.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1417142 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 708196

African (AFR) AF: 0.00 AC: 0 AN: 32442

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25898

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00 AC: 0 AN: 85318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1071372

Other (OTH) AF: 0.00 AC: 0 AN: 58914

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.52
PhyloP100		-0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2294100; hg19: chr8-42175303;