chr1-206474379-C-T

Variant names:

• chr1-206474379-C-T
• rs56035621
• ENST00000584998.5:c.-120C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001193321.2(IKBKE):​c.-120C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,614,102 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00096 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (6 hom.)
• Consequence: IKBKE NM_001193321.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.76
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 1-206474379-C-T is Benign according to our data. Variant chr1-206474379-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193321.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	NM_014002.4	MANE Select	c.136C>T	p.Leu46Leu	synonymous	Exon 4 of 22	NP_054721.1	Q14164-1
	IKBKE	NM_001193321.2		c.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 21	NP_001180250.1	Q14164-2
	IKBKE	NM_001193322.2		c.136C>T	p.Leu46Leu	synonymous	Exon 4 of 21	NP_001180251.1	A0A075B7B4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	ENST00000584998.5	TSL:1	c.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 21	ENSP00000462396.1	Q14164-2
	IKBKE	ENST00000581977.7	TSL:1 MANE Select	c.136C>T	p.Leu46Leu	synonymous	Exon 4 of 22	ENSP00000464030.1	Q14164-1
	IKBKE	ENST00000578328.6	TSL:1	c.136C>T	p.Leu46Leu	synonymous	Exon 4 of 21	ENSP00000473833.1	A0A075B7B4

Frequencies

GnomAD3 genomes AF: 0.000959 AC: 146 AN: 152238 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00102 AC: 257 AN: 251314 AF XY: 0.00110

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00150

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.00153 AC: 2231 AN: 1461746 Hom.: 6 Cov.: 30 AF XY: 0.00147 AC XY: 1072 AN XY: 727174

African (AFR) AF: 0.000358 AC: 12 AN: 33474

American (AMR) AF: 0.000157 AC: 7 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00213 AC: 184 AN: 86254

European-Finnish (FIN) AF: 0.000412 AC: 22 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00173 AC: 1919 AN: 1111906

Other (OTH) AF: 0.00142 AC: 86 AN: 60388

GnomAD4 genome AF: 0.000958 AC: 146 AN: 152356 Hom.: 1 Cov.: 32 AF XY: 0.000792 AC XY: 59 AN XY: 74504

African (AFR) AF: 0.000361 AC: 15 AN: 41570

American (AMR) AF: 0.000523 AC: 8 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4834

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00160 AC: 109 AN: 68036

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.000778

EpiCase AF: 0.00153

EpiControl AF: 0.00154

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.5
DANN	Benign	0.64
PhyloP100		1.8

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: rs56035621; hg19: chr1-206647722; COSMIC: COSV100898408; COSMIC: COSV100898408;