rs17433930

Variant names:

• chr1-206479396-A-G
• rs17433930
• NM_014002.4:c.1183+263A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-206479396-A-G
• chr1-206479396-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014002.4(IKBKE):​c.1183+263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 152,126 control chromosomes in the GnomAD database, including 355 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 0.057 (355 hom., cov: 31)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 3 publications found

Genes affected

IKBKE (HGNC:14552): (inhibitor of nuclear factor kappa B kinase subunit epsilon) IKBKE is a noncanonical I-kappa-B (see MIM 164008) kinase (IKK) that is essential for regulating antiviral signaling pathways. IKBKE has also been identified as a breast cancer (MIM 114480) oncogene and is amplified and overexpressed in over 30% of breast carcinomas and breast cancer cell lines (Hutti et al., 2009 [PubMed 19481526]).[supplied by OMIM, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014002.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	NM_014002.4	MANE Select	c.1183+263A>G		intron	N/A	NP_054721.1
	IKBKE	NM_001193322.2		c.1183+263A>G		intron	N/A	NP_001180251.1
	IKBKE	NM_001193321.2		c.928+263A>G		intron	N/A	NP_001180250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	ENST00000581977.7	TSL:1 MANE Select	c.1183+263A>G		intron	N/A	ENSP00000464030.1
	IKBKE	ENST00000578328.6	TSL:1	c.1183+263A>G		intron	N/A	ENSP00000473833.1
	IKBKE	ENST00000584998.5	TSL:1	c.928+263A>G		intron	N/A	ENSP00000462396.1

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 8607 AN: 152008 Hom.: 355 Cov.: 31

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0566 AC: 8606 AN: 152126 Hom.: 355 Cov.: 31 AF XY: 0.0578 AC XY: 4297 AN XY: 74332

African (AFR) AF: 0.0129 AC: 534 AN: 41508

American (AMR) AF: 0.0545 AC: 832 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3470

East Asian (EAS) AF: 0.0130 AC: 67 AN: 5172

South Asian (SAS) AF: 0.0764 AC: 368 AN: 4818

European-Finnish (FIN) AF: 0.0907 AC: 959 AN: 10572

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5271 AN: 67994

Other (OTH) AF: 0.0558 AC: 118 AN: 2114

Alfa AF: 0.0528 Hom.: 146

Bravo AF: 0.0517

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.51
PhyloP100		-1.5

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: rs17433930; hg19: chr1-206652739;