rs12409804

Variant names:

• chr1-206483839-T-A
• rs12409804
• NM_014002.4:c.1428-1158T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-206483839-T-A
• chr1-206483839-T-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.1428-1158T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,186 control chromosomes in the GnomAD database, including 5,318 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 (5318 hom., cov: 33)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKBKE	NM_014002.4	c.1428-1158T>A		intron_variant	Intron 13 of 21	ENST00000581977.7	NP_054721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKBKE	ENST00000581977.7	c.1428-1158T>A		intron_variant	Intron 13 of 21	1	NM_014002.4	ENSP00000464030.1
IKBKE	ENST00000578328.6	c.1428-1158T>A		intron_variant	Intron 13 of 20	1		ENSP00000473833.1
IKBKE	ENST00000584998.5	c.1173-1158T>A		intron_variant	Intron 12 of 20	1		ENSP00000462396.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37718 AN: 152068 Hom.: 5321 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.248 AC: 37713 AN: 152186 Hom.: 5318 Cov.: 33 AF XY: 0.255 AC XY: 18988 AN XY: 74390

African (AFR) AF: 0.184 AC: 7625 AN: 41528

American (AMR) AF: 0.326 AC: 4977 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 793 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3272 AN: 5172

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4820

European-Finnish (FIN) AF: 0.258 AC: 2737 AN: 10596

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16167 AN: 67994

Other (OTH) AF: 0.288 AC: 609 AN: 2114

Alfa AF: 0.236 Hom.: 621

Bravo AF: 0.255

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.33
PhyloP100		-0.11

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: rs12409804; hg19: chr1-206657181;