1-206476609-G-A

Position:

• chr1-206476609-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKE	NM_014002.4	c.541-69G>A		intron_variant		ENST00000581977.7	NP_054721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKBKE	ENST00000581977.7	c.541-69G>A		intron_variant		1	NM_014002.4	ENSP00000464030	P1
IKBKE	ENST00000578328.6	c.541-69G>A		intron_variant		1		ENSP00000473833
IKBKE	ENST00000584998.5	c.286-69G>A		intron_variant		1		ENSP00000462396
IKBKE	ENST00000605818.5	n.886-69G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.618

Gnomad4 AMR exome AF: 0.0842

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.0533

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.152

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

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0351

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.215

Alfa AF: 0.142 Hom.: 2302

Bravo AF: 0.265

Asia WGS AF: 0.164 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11117909; hg19: chr1-206649952;