1-206474444-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014002.4(IKBKE):c.201T>C(p.Ile67=) 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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKE	NM_014002.4	c.201T>C	p.Ile67=	synonymous_variant	4/22	ENST00000581977.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKBKE	ENST00000581977.7	c.201T>C	p.Ile67=	synonymous_variant	4/22	1	NM_014002.4	P1

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

GnomAD3 exomes AF: 0.861 AC: 215982 AN: 250756 Hom.: 93353 AF XY: 0.859 AC XY: 116415 AN XY: 135538

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 SAS exome AF: 0.869

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

Gnomad4 AFR exome AF: 0.874

Gnomad4 AMR exome AF: 0.925

Gnomad4 ASJ exome AF: 0.780

Gnomad4 EAS exome AF: 0.961

Gnomad4 SAS exome AF: 0.867

Gnomad4 FIN exome AF: 0.827

Gnomad4 NFE exome AF: 0.838

Gnomad4 OTH exome AF: 0.851

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

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.836

Gnomad4 OTH AF: 0.867

Alfa AF: 0.839 Hom.: 86758

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	5.8
Dann	Benign	0.62

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: rs1539243; hg19: chr1-206647787;