rs782265530

Variant names:

• chr1-206476727-C-A
• rs782265530
• NM_014002.4:c.590C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-206476727-C-A
• chr1-206476727-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014002.4(IKBKE):​c.590C>A​(p.Ala197Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A197V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IKBKE NM_014002.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34961185).

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.590C>A	p.Ala197Glu	missense	Exon 7 of 22	NP_054721.1	Q14164-1
	IKBKE	NM_001193322.2		c.590C>A	p.Ala197Glu	missense	Exon 7 of 21	NP_001180251.1	A0A075B7B4
	IKBKE	NM_001193321.2		c.335C>A	p.Ala112Glu	missense	Exon 6 of 21	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.590C>A	p.Ala197Glu	missense	Exon 7 of 22	ENSP00000464030.1	Q14164-1
	IKBKE	ENST00000578328.6	TSL:1	c.590C>A	p.Ala197Glu	missense	Exon 7 of 21	ENSP00000473833.1	A0A075B7B4
	IKBKE	ENST00000584998.5	TSL:1	c.335C>A	p.Ala112Glu	missense	Exon 6 of 21	ENSP00000462396.1	Q14164-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.37	N
PhyloP100		2.4
PrimateAI	Benign	0.46	T
Sift4G	Benign	0.11	T
Polyphen		0.32	B
Vest4		0.40
MutPred		0.51		Gain of solvent accessibility (P = 0.0261)
MVP		0.47
ClinPred		0.87	D
GERP RS		5.1
Varity_R		0.17
gMVP		0.61
Mutation Taster		=100/0	polymorphism

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: rs782265530; hg19: chr1-206650070;