chr1-206487185-G-A

Position:

• chr1-206487185-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.1617-729G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,316 control chromosomes in the GnomAD database, including 1,346 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 0.11 (1346 hom., cov: 32)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKE	NM_014002.4	c.1617-729G>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.1617-729G>A		intron_variant		1	NM_014002.4	ENSP00000464030	P1
IKBKE	ENST00000578328.6	c.1617-729G>A		intron_variant		1		ENSP00000473833
IKBKE	ENST00000584998.5	c.1362-729G>A		intron_variant		1		ENSP00000462396

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17446 AN: 152196 Hom.: 1347 Cov.: 32

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.115 AC: 17443 AN: 152316 Hom.: 1346 Cov.: 32 AF XY: 0.113 AC XY: 8444 AN XY: 74474

Gnomad4 AFR AF: 0.0262

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.126

Alfa AF: 0.131 Hom.: 206

Bravo AF: 0.104

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs12728136; hg19: chr1-206660522;