1-206473323-C-G

Variant names:

• chr1-206473323-C-G
• rs41295990
• NM_014002.4:c.87+9C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014002.4(IKBKE):​c.87+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,450,942 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: IKBKE NM_014002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	NM_014002.4	MANE Select	c.87+9C>G		intron	N/A	NP_054721.1	Q14164-1
	IKBKE	NM_001193322.2		c.87+9C>G		intron	N/A	NP_001180251.1	A0A075B7B4
	IKBKE	NM_001193321.2		c.-168-1008C>G		intron	N/A	NP_001180250.1	Q14164-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IKBKE	ENST00000581977.7	TSL:1 MANE Select	c.87+9C>G		intron	N/A	ENSP00000464030.1	Q14164-1
	IKBKE	ENST00000578328.6	TSL:1	c.87+9C>G		intron	N/A	ENSP00000473833.1	A0A075B7B4
	IKBKE	ENST00000584998.5	TSL:1	c.-168-1008C>G		intron	N/A	ENSP00000462396.1	Q14164-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 235378 AF XY: 0.0000235

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000283

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1450942 Hom.: 0 Cov.: 29 AF XY: 0.00000554 AC XY: 4 AN XY: 721558

African (AFR) AF: 0.00 AC: 0 AN: 33262

American (AMR) AF: 0.00 AC: 0 AN: 43898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25854

East Asian (EAS) AF: 0.00 AC: 0 AN: 39440

South Asian (SAS) AF: 0.00 AC: 0 AN: 84800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1105202

Other (OTH) AF: 0.00 AC: 0 AN: 60006

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.56
PromoterAI		-0.015	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs41295990; hg19: chr1-206646666;