rs1059704

chr1-206475035-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014002.4(IKBKE):c.358+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,607,262 control chromosomes in the GnomAD database, including 355,973 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 0.58 (27170 hom., cov: 31)
  • Exomes 𝑓: 0.67 (328803 hom.)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKE	NM_014002.4	c.358+41G>A		intron_variant		ENST00000581977.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IKBKE	ENST00000581977.7	c.358+41G>A		intron_variant		1	NM_014002.4	P1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88583 AN: 151884 Hom.: 27170 Cov.: 31

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.602

GnomAD3 exomes AF: 0.622 AC: 154526 AN: 248360 Hom.: 49527 AF XY: 0.630 AC XY: 84582 AN XY: 134234

Gnomad AFR exome AF: 0.403

Gnomad AMR exome AF: 0.640

Gnomad ASJ exome AF: 0.627

Gnomad EAS exome AF: 0.334

Gnomad SAS exome AF: 0.661

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.631

GnomAD4 exome AF: 0.668 AC: 971506 AN: 1455260 Hom.: 328803 Cov.: 33 AF XY: 0.668 AC XY: 483112 AN XY: 723376

Gnomad4 AFR exome AF: 0.389

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.628

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.633

Gnomad4 NFE exome AF: 0.694

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.583 AC: 88627 AN: 152002 Hom.: 27170 Cov.: 31 AF XY: 0.578 AC XY: 42965 AN XY: 74284

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.602

Alfa AF: 0.637 Hom.: 8822

Bravo AF: 0.569

Asia WGS AF: 0.479 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.3
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1059704; hg19: chr1-206648378; COSMIC: COSV65624186; COSMIC: COSV65624186;