rs17433930

chr1-206479396-A-Gchr1-206479396-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKE	NM_014002.4	c.1183+263A>G		intron_variant		ENST00000581977.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKBKE	ENST00000581977.7	c.1183+263A>G		intron_variant		1	NM_014002.4	P1
IKBKE	ENST00000578328.6	c.1183+263A>G		intron_variant		1
IKBKE	ENST00000584998.5	c.928+263A>G		intron_variant		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

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.0764

Gnomad4 FIN AF: 0.0907

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0684 Hom.: 102

Bravo AF: 0.0517

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.32
Dann	Benign	0.51

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: rs17433930; hg19: chr1-206652739;