1-206486023-G-C

Variant names:

• chr1-206486023-G-C
• rs11118132
• NM_014002.4:c.1616+717G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014002.4(IKBKE):​c.1616+717G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,092 control chromosomes in the GnomAD database, including 21,640 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 0.50 (21640 hom., cov: 33)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKBKE	NM_014002.4	c.1616+717G>C		intron_variant	Intron 15 of 21	ENST00000581977.7	NP_054721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKBKE	ENST00000581977.7	c.1616+717G>C		intron_variant	Intron 15 of 21	1	NM_014002.4	ENSP00000464030.1
IKBKE	ENST00000578328.6	c.1616+717G>C		intron_variant	Intron 15 of 20	1		ENSP00000473833.1
IKBKE	ENST00000584998.5	c.1361+717G>C		intron_variant	Intron 14 of 20	1		ENSP00000462396.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75493 AN: 151974 Hom.: 21601 Cov.: 33

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.496

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75587 AN: 152092 Hom.: 21640 Cov.: 33 AF XY: 0.501 AC XY: 37233 AN XY: 74356

African (AFR) AF: 0.783 AC: 32527 AN: 41520

American (AMR) AF: 0.464 AC: 7089 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1258 AN: 3464

East Asian (EAS) AF: 0.669 AC: 3461 AN: 5170

South Asian (SAS) AF: 0.420 AC: 2024 AN: 4820

European-Finnish (FIN) AF: 0.374 AC: 3958 AN: 10578

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23736 AN: 67962

Other (OTH) AF: 0.500 AC: 1053 AN: 2106

Alfa AF: 0.287 Hom.: 825

Bravo AF: 0.519

Asia WGS AF: 0.589 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.078
DANN	Benign	0.42
PhyloP100		-1.7

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: rs11118132; hg19: chr1-206659360; COSMIC: COSV65624885;