Genetic Variant CHUK:c.2209-246G>A (chr10-100186688-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001441063.1(CHUK):c.2209-246G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 152,050 control chromosomes in the GnomAD database, including 790 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 0.076 ( 790 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHUK
NM_001441063.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.304

Publications

5 publications found

Variant links:

Genes affected

CHUK (HGNC:1974): (component of inhibitor of nuclear factor kappa B kinase complex) This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor. [provided by RefSeq, Jul 2008]

CHUK Gene-Disease associations (from GenCC):

cocoon syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
Bartsocas-Papas syndrome 2
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

CHUK links:

ENSG00000305493 (HGNC:):

ENSG00000305493 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHUK	NM_001441063.1 link	c.2209-246G>A		intron_variant	Intron 20 of 20		NP_001427992.1
CHUK	XM_047424542.1 link	c.*32-246G>A		intron_variant	Intron 20 of 20		XP_047280498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000305493	ENST00000811302.1 link	n.*205C>T		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0758

AC:

11518

AN:

151932

Hom.:

774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.0617

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.0952

Gnomad SAS

AF:

0.0745

Gnomad FIN

AF:

0.0746

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0708

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0761

AC:

11574

AN:

152050

Hom.:

790

Cov.:

AF XY:

0.0803

AC XY:

5966

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.176

AC:

7288

AN:

41438

American (AMR)

AF:

0.0617

AC:

942

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

AN:

3468

East Asian (EAS)

AF:

0.0949

AC:

491

AN:

5176

South Asian (SAS)

AF:

0.0739

AC:

356

AN:

4816

European-Finnish (FIN)

AF:

0.0746

AC:

788

AN:

10560

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0206

AC:

1404

AN:

68000

Other (OTH)

AF:

0.0701

AC:

148

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

523

1045

1568

2090

2613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0495

Hom.:

265

Bravo

AF:

0.0799

Asia WGS

AF:

0.0970

AC:

335

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.8

(source)

DANN

Benign

0.87

PhyloP100

0.30

Mutation Taster

=300/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over