dbSNP rs17112751: CHUK:c.475-137A>G (chr10-100219496-T-C) – ACMG Classification: Benign (-20 pts)

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.475-137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 641,502 control chromosomes in the GnomAD database, including 1,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 787 hom., cov: 32)

Exomes 𝑓: 0.041 ( 774 hom. )

Consequence

CHUK
NM_001278.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.44

Publications

2 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 (BayesDel_noAF=-0.94).

BP6

Variant 10-100219496-T-C is Benign according to our data. Variant chr10-100219496-T-C is described in ClinVar as Benign. ClinVar VariationId is 1288291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHUK	NM_001278.5 link	c.475-137A>G		intron_variant	Intron 5 of 20	ENST00000370397.8	NP_001269.3	O15111

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHUK	ENST00000370397.8 link	c.475-137A>G		intron_variant	Intron 5 of 20	1	NM_001278.5	ENSP00000359424.6		O15111

Frequencies

GnomAD3 genomes

AF:

0.0759

AC:

11543

AN:

152054

Hom.:

771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0617

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.0963

Gnomad SAS

AF:

0.0745

Gnomad FIN

AF:

0.0742

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0711

GnomAD4 exome

AF:

0.0415

AC:

20285

AN:

489330

Hom.:

774

AF XY:

0.0417

AC XY:

10939

AN XY:

262474

show subpopulations

African (AFR)

AF:

0.181

AC:

2396

AN:

13270

American (AMR)

AF:

0.0654

AC:

1542

AN:

23584

Ashkenazi Jewish (ASJ)

AF:

0.0212

AC:

335

AN:

15828

East Asian (EAS)

AF:

0.0963

AC:

3033

AN:

31508

South Asian (SAS)

AF:

0.0704

AC:

3615

AN:

51322

European-Finnish (FIN)

AF:

0.0674

AC:

2206

AN:

32742

Middle Eastern (MID)

AF:

0.0635

AC:

135

AN:

2126

European-Non Finnish (NFE)

AF:

0.0197

AC:

5742

AN:

291420

Other (OTH)

AF:

0.0465

AC:

1281

AN:

27530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

939

1878

2817

3756

4695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.0762

AC:

11599

AN:

152172

Hom.:

787

Cov.:

AF XY:

0.0804

AC XY:

5980

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.176

AC:

7304

AN:

41496

American (AMR)

AF:

0.0617

AC:

944

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0207

AC:

AN:

3472

East Asian (EAS)

AF:

0.0959

AC:

497

AN:

5182

South Asian (SAS)

AF:

0.0739

AC:

356

AN:

4816

European-Finnish (FIN)

AF:

0.0742

AC:

787

AN:

10602

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0207

AC:

1406

AN:

67998

Other (OTH)

AF:

0.0703

AC:

148

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

514

1027

1541

2054

2568

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:

0.0577

Hom.:

111

Bravo

AF:

0.0801

Asia WGS

AF:

0.0970

AC:

335

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.20

(source)

DANN

Benign

0.30

PhyloP100

-1.4

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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