1-206476714-C-T

Variant names:

• chr1-206476714-C-T
• rs2103455807
• NM_014002.4:c.577C>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.577C>T​(p.Pro193Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IKBKE NM_014002.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67
• 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=0.3592916).

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.577C>T	p.Pro193Ser	missense	Exon 7 of 22	NP_054721.1	Q14164-1
	IKBKE	NM_001193322.2		c.577C>T	p.Pro193Ser	missense	Exon 7 of 21	NP_001180251.1	A0A075B7B4
	IKBKE	NM_001193321.2		c.322C>T	p.Pro108Ser	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.577C>T	p.Pro193Ser	missense	Exon 7 of 22	ENSP00000464030.1	Q14164-1
	IKBKE	ENST00000578328.6	TSL:1	c.577C>T	p.Pro193Ser	missense	Exon 7 of 21	ENSP00000473833.1	A0A075B7B4
	IKBKE	ENST00000584998.5	TSL:1	c.322C>T	p.Pro108Ser	missense	Exon 6 of 21	ENSP00000462396.1	Q14164-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 26136

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: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.7
PrimateAI	Uncertain	0.60	T
Sift4G	Benign	0.23	T
Polyphen		0.93	P
Vest4		0.52
MutPred		0.30		Gain of MoRF binding (P = 0.047)
MVP		0.65
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.20
gMVP		0.72
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: rs2103455807; hg19: chr1-206650057;