Genetic Variant IKBKE:c.541-69G>A (chr1-206476609-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000581977.7(IKBKE):c.541-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,568,682 control chromosomes in the GnomAD database, including 25,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.25 ( 8288 hom., cov: 33)

Exomes 𝑓: 0.13 ( 17359 hom. )

Consequence

IKBKE
ENST00000581977.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.933

Publications

13 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000581977.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IKBKE	NM_014002.4	MANE Select	c.541-69G>A	intron	N/A	NP_054721.1
IKBKE	NM_001193322.2		c.541-69G>A	intron	N/A	NP_001180251.1
IKBKE	NM_001193321.2		c.286-69G>A	intron	N/A	NP_001180250.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IKBKE	ENST00000581977.7	TSL:1 MANE Select	c.541-69G>A	intron	N/A	ENSP00000464030.1
IKBKE	ENST00000578328.6	TSL:1	c.541-69G>A	intron	N/A	ENSP00000473833.1
IKBKE	ENST00000584998.5	TSL:1	c.286-69G>A	intron	N/A	ENSP00000462396.1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38268

AN:

152118

Hom.:

8255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.588

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.0352

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.133

AC:

188402

AN:

1416446

Hom.:

17359

AF XY:

0.133

AC XY:

93595

AN XY:

704870

show subpopulations

African (AFR)

AF:

0.618

AC:

20078

AN:

32466

American (AMR)

AF:

0.0842

AC:

3600

AN:

42750

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3416

AN:

25026

East Asian (EAS)

AF:

0.0533

AC:

2088

AN:

39176

South Asian (SAS)

AF:

0.178

AC:

14847

AN:

83458

European-Finnish (FIN)

AF:

0.141

AC:

7322

AN:

52084

Middle Eastern (MID)

AF:

0.135

AC:

755

AN:

5594

European-Non Finnish (NFE)

AF:

0.118

AC:

127379

AN:

1077352

Other (OTH)

AF:

0.152

AC:

8917

AN:

58540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

7921

15842

23764

31685

39606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4738

9476

14214

18952

23690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.252

AC:

38356

AN:

152236

Hom.:

8288

Cov.:

AF XY:

0.248

AC XY:

18430

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.589

AC:

24445

AN:

41514

American (AMR)

AF:

0.142

AC:

2171

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

485

AN:

3472

East Asian (EAS)

AF:

0.0351

AC:

182

AN:

5188

South Asian (SAS)

AF:

0.164

AC:

790

AN:

4826

European-Finnish (FIN)

AF:

0.144

AC:

1523

AN:

10602

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8094

AN:

68014

Other (OTH)

AF:

0.215

AC:

454

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1162

2324

3487

4649

5811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.168

Hom.:

9701

Bravo

AF:

0.265

Asia WGS

AF:

0.164

AC:

573

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.14

(source)

DANN

Benign

0.64

PhyloP100

-0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.36

Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over