dbSNP rs1059704: IKBKE:c.358+41G>A (chr1-206475035-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014002.4(IKBKE):c.358+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,607,262 control chromosomes in the GnomAD database, including 355,973 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 27170 hom., cov: 31)

Exomes 𝑓: 0.67 ( 328803 hom. )

Consequence

IKBKE
NM_014002.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.162

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:

MIR6769B (HGNC:50016): (microRNA 6769b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6769B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IKBKE	NM_014002.4 link	c.358+41G>A		intron_variant	Intron 5 of 21	ENST00000581977.7	NP_054721.1	Q14164-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IKBKE	ENST00000581977.7 link	c.358+41G>A		intron_variant	Intron 5 of 21	1	NM_014002.4	ENSP00000464030.1		Q14164-1

Frequencies

GnomAD3 genomes

AF:

0.583

AC:

88583

AN:

151884

Hom.:

27170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.634

Gnomad FIN

AF:

0.635

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.602

GnomAD3 exomes

AF:

0.622

AC:

154526

AN:

248360

Hom.:

49527

AF XY:

0.630

AC XY:

84582

AN XY:

134234

show subpopulations

Gnomad AFR exome

AF:

0.403

Gnomad AMR exome

AF:

0.640

Gnomad ASJ exome

AF:

0.627

Gnomad EAS exome

AF:

0.334

Gnomad SAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.636

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.631

GnomAD4 exome

AF:

0.668

AC:

971506

AN:

1455260

Hom.:

328803

Cov.:

AF XY:

0.668

AC XY:

483112

AN XY:

723376

show subpopulations

Gnomad4 AFR exome

AF:

0.389

Gnomad4 AMR exome

AF:

0.630

Gnomad4 ASJ exome

AF:

0.628

Gnomad4 EAS exome

AF:

0.370

Gnomad4 SAS exome

AF:

0.658

Gnomad4 FIN exome

AF:

0.633

Gnomad4 NFE exome

AF:

0.694

Gnomad4 OTH exome

AF:

0.631

GnomAD4 genome

AF:

0.583

AC:

88627

AN:

152002

Hom.:

27170

Cov.:

AF XY:

0.578

AC XY:

42965

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.604

Gnomad4 ASJ

AF:

0.612

Gnomad4 EAS

AF:

0.359

Gnomad4 SAS

AF:

0.634

Gnomad4 FIN

AF:

0.635

Gnomad4 NFE

AF:

0.688

Gnomad4 OTH

AF:

0.602

Alfa

AF:

0.637

Hom.:

8822

Bravo

AF:

0.569

Asia WGS

AF:

0.479

AC:

1666

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.3

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over