Genetic Variant NM_014002.4:c.87+9C>A (chr1-206473323-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014002.4(IKBKE):c.87+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,603,296 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 14 hom. )

Consequence

IKBKE
NM_014002.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.561

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 1-206473323-C-A is Benign according to our data. Variant chr1-206473323-C-A is described in ClinVar as Benign. ClinVar VariationId is 720904.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00723 (1102/152370) while in subpopulation AFR AF = 0.0256 (1063/41600). AF 95% confidence interval is 0.0243. There are 15 homozygotes in GnomAd4. There are 513 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IKBKE	NM_014002.4	MANE Select	c.87+9C>A	intron	N/A	NP_054721.1	Q14164-1
IKBKE	NM_001193322.2		c.87+9C>A	intron	N/A	NP_001180251.1	A0A075B7B4
IKBKE	NM_001193321.2		c.-168-1008C>A	intron	N/A	NP_001180250.1	Q14164-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IKBKE	ENST00000581977.7	TSL:1 MANE Select	c.87+9C>A	intron	N/A	ENSP00000464030.1	Q14164-1
IKBKE	ENST00000578328.6	TSL:1	c.87+9C>A	intron	N/A	ENSP00000473833.1	A0A075B7B4
IKBKE	ENST00000584998.5	TSL:1	c.-168-1008C>A	intron	N/A	ENSP00000462396.1	Q14164-2

Frequencies

GnomAD3 genomes

AF:

0.00723

AC:

1101

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

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:

0.0000294

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00170

AC:

400

AN:

235378

AF XY:

0.00120

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.000846

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000283

Gnomad OTH exome

AF:

0.000525

GnomAD4 exome

AF:

0.000687

AC:

997

AN:

1450926

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

444

AN XY:

721546

show subpopulations

African (AFR)

AF:

0.0257

AC:

855

AN:

33250

American (AMR)

AF:

0.00109

AC:

AN:

43896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25854

East Asian (EAS)

AF:

0.00

AC:

AN:

39440

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52730

Middle Eastern (MID)

AF:

0.000522

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000199

AC:

AN:

1105200

Other (OTH)

AF:

0.00113

AC:

AN:

60006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00723

AC:

1102

AN:

152370

Hom.:

Cov.:

AF XY:

0.00689

AC XY:

513

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0256

AC:

1063

AN:

41600

American (AMR)

AF:

0.00176

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68036

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

142

190

237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00356

Hom.:

Bravo

AF:

0.00771

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.56

PromoterAI

-0.025

Neutral

(source)

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

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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