Variant 1-206476673-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014002.4(IKBKE):c.541-5G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

IKBKE
NM_014002.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.4998

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -2.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IKBKE	NM_014002.4 linkuse as main transcript	c.541-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000581977.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
IKBKE	ENST00000581977.7 linkuse as main transcript	c.541-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_014002.4	P1	Q14164-1
IKBKE	ENST00000578328.6 linkuse as main transcript	c.541-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1
IKBKE	ENST00000584998.5 linkuse as main transcript	c.286-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1			Q14164-2
IKBKE	ENST00000605818.5 linkuse as main transcript	n.886-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000519

AC:

AN:

250358

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135428

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000144

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autoimmune connective tissue disease and vasculitis

Uncertain:1

Uncertain significance, flagged submission

clinical testing

Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital

Oct 04, 2020

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital

Dec 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

5.7

Dann

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.50

dbscSNV1_RF

Benign

0.59

SpliceAI score (max)

0.96

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.96

Position offset: 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