Variant 1-206477810-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014002.4(IKBKE):c.763G>A(p.Gly255Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,408,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

IKBKE
NM_014002.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.87

Variant links:

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]

IKBKE links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IKBKE	NM_014002.4 linkuse as main transcript	c.763G>A	p.Gly255Arg	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 linkuse as main transcript	c.763G>A	p.Gly255Arg	missense_variant	8/22	1	NM_014002.4	ENSP00000464030	P1	Q14164-1
IKBKE	ENST00000578328.6 linkuse as main transcript	c.763G>A	p.Gly255Arg	missense_variant	8/21	1		ENSP00000473833
IKBKE	ENST00000584998.5 linkuse as main transcript	c.508G>A	p.Gly170Arg	missense_variant	7/21	1		ENSP00000462396		Q14164-2
IKBKE	ENST00000605818.5 linkuse as main transcript	n.1108G>A		non_coding_transcript_exon_variant	8/8	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000284

AC:

AN:

1408704

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695980

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000539

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 25, 2022

The c.763G>A (p.G255R) alteration is located in exon 8 (coding exon 6) of the IKBKE gene. This alteration results from a G to A substitution at nucleotide position 763, causing the glycine (G) at amino acid position 255 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

.;.;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Uncertain

0.19

MutationAssessor

Uncertain

2.6

.;.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.83

MutPred

0.56

Gain of solvent accessibility (P = 0.0789);.;Gain of solvent accessibility (P = 0.0789);

MVP

0.96

ClinPred

0.91

GERP RS

4.9

Varity_R

0.36

gMVP

0.80

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over