1-206477834-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014002.4(IKBKE):c.787C>T(p.Leu263Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,555,782 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )
Consequence
IKBKE
NM_014002.4 missense
NM_014002.4 missense
Scores
2
8
6
Clinical Significance
Conservation
PhyloP100: 1.17
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19278201).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IKBKE | NM_014002.4 | c.787C>T | p.Leu263Phe | missense_variant | 8/22 | ENST00000581977.7 | NP_054721.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IKBKE | ENST00000581977.7 | c.787C>T | p.Leu263Phe | missense_variant | 8/22 | 1 | NM_014002.4 | ENSP00000464030 | P1 | |
IKBKE | ENST00000578328.6 | c.787C>T | p.Leu263Phe | missense_variant | 8/21 | 1 | ENSP00000473833 | |||
IKBKE | ENST00000584998.5 | c.532C>T | p.Leu178Phe | missense_variant | 7/21 | 1 | ENSP00000462396 | |||
IKBKE | ENST00000605818.5 | n.1132C>T | non_coding_transcript_exon_variant | 8/8 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000310 AC: 5AN: 161484Hom.: 0 AF XY: 0.0000350 AC XY: 3AN XY: 85750
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GnomAD4 exome AF: 0.0000242 AC: 34AN: 1403596Hom.: 0 Cov.: 31 AF XY: 0.0000188 AC XY: 13AN XY: 693116
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2024 | The c.787C>T (p.L263F) alteration is located in exon 8 (coding exon 6) of the IKBKE gene. This alteration results from a C to T substitution at nucleotide position 787, causing the leucine (L) at amino acid position 263 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Uncertain
.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;.;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;.;D
Vest4
MutPred
Gain of loop (P = 0.0435);.;Gain of loop (P = 0.0435);
MVP
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at