rs11591741

Variant names:

• chr10-100216744-G-C
• rs11591741
• NM_001278.5:c.933+1251C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278.5(CHUK):​c.933+1251C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,060 control chromosomes in the GnomAD database, including 8,189 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 0.30 (8189 hom., cov: 32)
• Consequence: CHUK NM_001278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 47 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, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Bartsocas-Papas syndrome 2

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHUK	NM_001278.5	MANE Select	c.933+1251C>G		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.933+1251C>G		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.933+1251C>G		intron	N/A	NP_001427992.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHUK	ENST00000370397.8	TSL:1 MANE Select	c.933+1251C>G		intron	N/A	ENSP00000359424.6	O15111
	CHUK	ENST00000896937.1		c.933+1251C>G		intron	N/A	ENSP00000566996.1
	CHUK	ENST00000896938.1		c.933+1251C>G		intron	N/A	ENSP00000566997.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45301 AN: 151942 Hom.: 8191 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45293 AN: 152060 Hom.: 8189 Cov.: 32 AF XY: 0.291 AC XY: 21596 AN XY: 74318

African (AFR) AF: 0.117 AC: 4869 AN: 41496

American (AMR) AF: 0.301 AC: 4603 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3472

East Asian (EAS) AF: 0.0658 AC: 341 AN: 5182

South Asian (SAS) AF: 0.156 AC: 755 AN: 4830

European-Finnish (FIN) AF: 0.326 AC: 3436 AN: 10542

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29087 AN: 67938

Other (OTH) AF: 0.313 AC: 661 AN: 2110

Alfa AF: 0.370 Hom.: 1638

Bravo AF: 0.287

Asia WGS AF: 0.116 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.65
DANN	Benign	0.57
PhyloP100		-0.034
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: rs11591741; hg19: chr10-101976501;