rs2151222

Variant names:

• chr1-206480926-A-G
• rs2151222
• NM_014002.4:c.1427+393A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-206480926-A-G
• chr1-206480926-A-T

Variant summary

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

The NM_014002.4(IKBKE):​c.1427+393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,096 control chromosomes in the GnomAD database, including 6,664 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 0.28 (6664 hom., cov: 32)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKBKE	NM_014002.4	c.1427+393A>G		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.1427+393A>G		intron_variant	Intron 13 of 21	1	NM_014002.4	ENSP00000464030.1
IKBKE	ENST00000578328.6	c.1427+393A>G		intron_variant	Intron 13 of 20	1		ENSP00000473833.1
IKBKE	ENST00000584998.5	c.1172+393A>G		intron_variant	Intron 12 of 20	1		ENSP00000462396.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43057 AN: 151978 Hom.: 6665 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.283 AC: 43073 AN: 152096 Hom.: 6664 Cov.: 32 AF XY: 0.291 AC XY: 21657 AN XY: 74366

African (AFR) AF: 0.251 AC: 10409 AN: 41478

American (AMR) AF: 0.356 AC: 5445 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3468

East Asian (EAS) AF: 0.627 AC: 3240 AN: 5168

South Asian (SAS) AF: 0.328 AC: 1581 AN: 4824

European-Finnish (FIN) AF: 0.280 AC: 2965 AN: 10594

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17549 AN: 67972

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.262 Hom.: 799

Bravo AF: 0.291

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.26
PhyloP100		-0.40

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

Other links and lift over

dbSNP: rs2151222; hg19: chr1-206654268;