NM_001278.5:c.475-137A>G

Variant names:

• chr10-100219496-T-C
• rs17112751
• NM_001278.5:c.475-137A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.44
• Publications: 2 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHUK	NM_001278.5	MANE Select	c.475-137A>G		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.475-137A>G		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.475-137A>G		intron	N/A	NP_001427992.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHUK	ENST00000370397.8	TSL:1 MANE Select	c.475-137A>G		intron	N/A	ENSP00000359424.6

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11543 AN: 152054 Hom.: 771 Cov.: 32

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

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

GnomAD4 genome AF: 0.0762 AC: 11599 AN: 152172 Hom.: 787 Cov.: 32 AF XY: 0.0804 AC XY: 5980 AN XY: 74418

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: 72 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: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1406 AN: 67998

Other (OTH) AF: 0.0703 AC: 148 AN: 2104

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.30
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17112751; hg19: chr10-101979253; COSMIC: COSV64917499;