rs11117909

Variant names:

• chr1-206476609-G-A
• rs11117909
• NM_014002.4:c.541-69G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-206476609-G-A
• chr1-206476609-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014002.4(IKBKE):​c.541-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,568,682 control chromosomes in the GnomAD database, including 25,647 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 0.25 (8288 hom., cov: 33)
  • Exomes 𝑓: 0.13 (17359 hom.)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933
• Publications: 13 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 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.541-69G>A		intron	N/A	NP_054721.1
	IKBKE	NM_001193322.2		c.541-69G>A		intron	N/A	NP_001180251.1
	IKBKE	NM_001193321.2		c.286-69G>A		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.541-69G>A		intron	N/A	ENSP00000464030.1
	IKBKE	ENST00000578328.6	TSL:1	c.541-69G>A		intron	N/A	ENSP00000473833.1
	IKBKE	ENST00000584998.5	TSL:1	c.286-69G>A		intron	N/A	ENSP00000462396.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38268 AN: 152118 Hom.: 8255 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0352

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.133 AC: 188402 AN: 1416446 Hom.: 17359 AF XY: 0.133 AC XY: 93595 AN XY: 704870

African (AFR) AF: 0.618 AC: 20078 AN: 32466

American (AMR) AF: 0.0842 AC: 3600 AN: 42750

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3416 AN: 25026

East Asian (EAS) AF: 0.0533 AC: 2088 AN: 39176

South Asian (SAS) AF: 0.178 AC: 14847 AN: 83458

European-Finnish (FIN) AF: 0.141 AC: 7322 AN: 52084

Middle Eastern (MID) AF: 0.135 AC: 755 AN: 5594

European-Non Finnish (NFE) AF: 0.118 AC: 127379 AN: 1077352

Other (OTH) AF: 0.152 AC: 8917 AN: 58540

GnomAD4 genome AF: 0.252 AC: 38356 AN: 152236 Hom.: 8288 Cov.: 33 AF XY: 0.248 AC XY: 18430 AN XY: 74424

African (AFR) AF: 0.589 AC: 24445 AN: 41514

American (AMR) AF: 0.142 AC: 2171 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3472

East Asian (EAS) AF: 0.0351 AC: 182 AN: 5188

South Asian (SAS) AF: 0.164 AC: 790 AN: 4826

European-Finnish (FIN) AF: 0.144 AC: 1523 AN: 10602

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8094 AN: 68014

Other (OTH) AF: 0.215 AC: 454 AN: 2112

Alfa AF: 0.168 Hom.: 9701

Bravo AF: 0.265

Asia WGS AF: 0.164 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.14
DANN	Benign	0.64
PhyloP100		-0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11117909; hg19: chr1-206649952;