1-206474107-A-G

Position:

• chr1-206474107-A-G

Variant summary

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

The NM_014002.4(IKBKE):​c.88-224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,056 control chromosomes in the GnomAD database, including 53,233 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 0.83 (53233 hom., cov: 30)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKE	NM_014002.4	c.88-224A>G		intron_variant		ENST00000581977.7	NP_054721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IKBKE	ENST00000581977.7	c.88-224A>G		intron_variant		1	NM_014002.4	ENSP00000464030	P1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126500 AN: 151934 Hom.: 53180 Cov.: 30

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.833 AC: 126621 AN: 152056 Hom.: 53233 Cov.: 30 AF XY: 0.825 AC XY: 61334 AN XY: 74304

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.806

Alfa AF: 0.833 Hom.: 52523

Bravo AF: 0.821

Asia WGS AF: 0.628 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1539241; hg19: chr1-206647450; COSMIC: COSV65627428; COSMIC: COSV65627428;