1-206474444-T-C

Variant names:

• chr1-206474444-T-C
• rs1539243
• NM_014002.4:c.201T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014002.4(IKBKE):​c.201T>C​(p.Ile67Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 1,613,530 control chromosomes in the GnomAD database, including 579,415 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 0.86 (55946 hom., cov: 32)
  • Exomes 𝑓: 0.85 (523469 hom.)
• Consequence: IKBKE NM_014002.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 47 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	NM_014002.4	MANE Select	c.201T>C	p.Ile67Ile	synonymous	Exon 4 of 22	NP_054721.1	Q14164-1
	IKBKE	NM_001193322.2		c.201T>C	p.Ile67Ile	synonymous	Exon 4 of 21	NP_001180251.1	A0A075B7B4
	IKBKE	NM_001193321.2		c.-55T>C		5_prime_UTR	Exon 3 of 21	NP_001180250.1	Q14164-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	ENST00000581977.7	TSL:1 MANE Select	c.201T>C	p.Ile67Ile	synonymous	Exon 4 of 22	ENSP00000464030.1	Q14164-1
	IKBKE	ENST00000578328.6	TSL:1	c.201T>C	p.Ile67Ile	synonymous	Exon 4 of 21	ENSP00000473833.1	A0A075B7B4
	IKBKE	ENST00000584998.5	TSL:1	c.-55T>C		5_prime_UTR	Exon 3 of 21	ENSP00000462396.1	Q14164-2

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130315 AN: 152134 Hom.: 55908 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.864

GnomAD2 exomes AF: 0.861 AC: 215982 AN: 250756 AF XY: 0.859

Gnomad AFR exome AF: 0.870

Gnomad AMR exome AF: 0.930

Gnomad ASJ exome AF: 0.777

Gnomad EAS exome AF: 0.977

Gnomad FIN exome AF: 0.830

Gnomad NFE exome AF: 0.833

Gnomad OTH exome AF: 0.843

GnomAD4 exome AF: 0.846 AC: 1235666 AN: 1461278 Hom.: 523469 Cov.: 44 AF XY: 0.845 AC XY: 614426 AN XY: 726932

African (AFR) AF: 0.874 AC: 29245 AN: 33464

American (AMR) AF: 0.925 AC: 41364 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 20390 AN: 26130

East Asian (EAS) AF: 0.961 AC: 38151 AN: 39698

South Asian (SAS) AF: 0.867 AC: 74775 AN: 86218

European-Finnish (FIN) AF: 0.827 AC: 44169 AN: 53378

Middle Eastern (MID) AF: 0.861 AC: 4964 AN: 5766

European-Non Finnish (NFE) AF: 0.838 AC: 931239 AN: 1111550

Other (OTH) AF: 0.851 AC: 51369 AN: 60380

GnomAD4 genome AF: 0.856 AC: 130403 AN: 152252 Hom.: 55946 Cov.: 32 AF XY: 0.857 AC XY: 63812 AN XY: 74426

African (AFR) AF: 0.872 AC: 36236 AN: 41554

American (AMR) AF: 0.892 AC: 13643 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2696 AN: 3472

East Asian (EAS) AF: 0.976 AC: 5068 AN: 5192

South Asian (SAS) AF: 0.883 AC: 4265 AN: 4828

European-Finnish (FIN) AF: 0.826 AC: 8750 AN: 10590

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56851 AN: 68000

Other (OTH) AF: 0.867 AC: 1832 AN: 2114

Alfa AF: 0.843 Hom.: 115056

Bravo AF: 0.863

Asia WGS AF: 0.926 AC: 3222 AN: 3478

EpiCase AF: 0.832

EpiControl AF: 0.830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.8
DANN	Benign	0.62
PhyloP100		-1.0

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: rs1539243; hg19: chr1-206647787; COSMIC: COSV108214656; COSMIC: COSV108214656;