rs1059704

Variant names:

• chr1-206475035-G-A
• rs1059704
• NM_014002.4:c.358+41G>A

Variant summary

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

The NM_014002.4(IKBKE):​c.358+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,607,262 control chromosomes in the GnomAD database, including 355,973 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 0.58 (27170 hom., cov: 31)
  • Exomes 𝑓: 0.67 (328803 hom.)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 12 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]

MIR6769B (HGNC:50016): (microRNA 6769b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014002.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	NM_014002.4	MANE Select	c.358+41G>A		intron	N/A	NP_054721.1
	IKBKE	NM_001193322.2		c.358+41G>A		intron	N/A	NP_001180251.1
	IKBKE	NM_001193321.2		c.103+41G>A		intron	N/A	NP_001180250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	ENST00000581977.7	TSL:1 MANE Select	c.358+41G>A		intron	N/A	ENSP00000464030.1
	IKBKE	ENST00000578328.6	TSL:1	c.358+41G>A		intron	N/A	ENSP00000473833.1
	IKBKE	ENST00000584998.5	TSL:1	c.103+41G>A		intron	N/A	ENSP00000462396.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88583 AN: 151884 Hom.: 27170 Cov.: 31

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.602

GnomAD2 exomes AF: 0.622 AC: 154526 AN: 248360 AF XY: 0.630

Gnomad AFR exome AF: 0.403

Gnomad AMR exome AF: 0.640

Gnomad ASJ exome AF: 0.627

Gnomad EAS exome AF: 0.334

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.631

GnomAD4 exome AF: 0.668 AC: 971506 AN: 1455260 Hom.: 328803 Cov.: 33 AF XY: 0.668 AC XY: 483112 AN XY: 723376

African (AFR) AF: 0.389 AC: 12976 AN: 33348

American (AMR) AF: 0.630 AC: 28057 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 16321 AN: 26004

East Asian (EAS) AF: 0.370 AC: 14659 AN: 39588

South Asian (SAS) AF: 0.658 AC: 56640 AN: 86032

European-Finnish (FIN) AF: 0.633 AC: 33656 AN: 53210

Middle Eastern (MID) AF: 0.570 AC: 2854 AN: 5006

European-Non Finnish (NFE) AF: 0.694 AC: 768412 AN: 1107468

Other (OTH) AF: 0.631 AC: 37931 AN: 60084

GnomAD4 genome AF: 0.583 AC: 88627 AN: 152002 Hom.: 27170 Cov.: 31 AF XY: 0.578 AC XY: 42965 AN XY: 74284

African (AFR) AF: 0.408 AC: 16905 AN: 41428

American (AMR) AF: 0.604 AC: 9220 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2124 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1852 AN: 5164

South Asian (SAS) AF: 0.634 AC: 3054 AN: 4818

European-Finnish (FIN) AF: 0.635 AC: 6710 AN: 10568

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46729 AN: 67966

Other (OTH) AF: 0.602 AC: 1268 AN: 2108

Alfa AF: 0.639 Hom.: 13190

Bravo AF: 0.569

Asia WGS AF: 0.479 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.79
PhyloP100		-0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1059704; hg19: chr1-206648378; COSMIC: COSV65624186; COSMIC: COSV65624186;