NM_001278.5:c.802G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001278.5(CHUK):c.802G>A(p.Val268Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,605,460 control chromosomes in the GnomAD database, including 213,829 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25191 hom., cov: 31)

Exomes 𝑓: 0.50 ( 188638 hom. )

Consequence

CHUK
NM_001278.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.14

Publications

66 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.5614154E-6).

BP6

Variant 10-100218126-C-T is Benign according to our data. Variant chr10-100218126-C-T is described in ClinVar as Benign. ClinVar VariationId is 1221248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHUK	NM_001278.5 link	c.802G>A	p.Val268Ile	missense_variant	Exon 9 of 21	ENST00000370397.8	NP_001269.3	O15111

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHUK	ENST00000370397.8 link	c.802G>A	p.Val268Ile	missense_variant	Exon 9 of 21	1	NM_001278.5	ENSP00000359424.6		O15111

Frequencies

GnomAD3 genomes

AF:

0.563

AC:

85443

AN:

151848

Hom.:

25155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.638

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.466

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.541

GnomAD2 exomes

AF:

0.474

AC:

118957

AN:

251076

AF XY:

0.468

show subpopulations

Gnomad AFR exome

AF:

0.751

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.487

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.488

GnomAD4 exome

AF:

0.504

AC:

732639

AN:

1453494

Hom.:

188638

Cov.:

AF XY:

0.499

AC XY:

360835

AN XY:

723620

show subpopulations

African (AFR)

AF:

0.758

AC:

25223

AN:

33272

American (AMR)

AF:

0.376

AC:

16787

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

11048

AN:

26082

East Asian (EAS)

AF:

0.480

AC:

19032

AN:

39646

South Asian (SAS)

AF:

0.336

AC:

28934

AN:

86124

European-Finnish (FIN)

AF:

0.462

AC:

24684

AN:

53406

Middle Eastern (MID)

AF:

0.469

AC:

2704

AN:

5760

European-Non Finnish (NFE)

AF:

0.519

AC:

573340

AN:

1104382

Other (OTH)

AF:

0.514

AC:

30887

AN:

60124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

16502

33004

49507

66009

82511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16434

32868

49302

65736

82170

<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:

0.563

AC:

85532

AN:

151966

Hom.:

25191

Cov.:

AF XY:

0.557

AC XY:

41328

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.750

AC:

31095

AN:

41456

American (AMR)

AF:

0.464

AC:

7074

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1502

AN:

3468

East Asian (EAS)

AF:

0.491

AC:

2529

AN:

5152

South Asian (SAS)

AF:

0.352

AC:

1695

AN:

4820

European-Finnish (FIN)

AF:

0.466

AC:

4921

AN:

10550

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.513

AC:

34838

AN:

67956

Other (OTH)

AF:

0.543

AC:

1144

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1829

3658

5487

7316

9145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.522

Hom.:

86039

Bravo

AF:

0.571

TwinsUK

AF:

0.529

AC:

1962

ALSPAC

AF:

0.516

AC:

1988

ESP6500AA

AF:

0.743

AC:

3274

ESP6500EA

AF:

0.501

AC:

4309

ExAC

AF:

0.479

AC:

58144

Asia WGS

AF:

0.462

AC:

1607

AN:

3478

EpiCase

AF:

0.509

EpiControl

AF:

0.514

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 74% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.066

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0000066

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.60

PhyloP100

3.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.67

REVEL

Benign

0.13

Sift

Benign

0.38

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.034

MPC

0.45

ClinPred

0.013

GERP RS

4.9

Varity_R

0.027

gMVP

0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over