10-100189834-CTTTTTTTTTT-CTTTTTTTTTTT

Variant names:

• chr10-100189834-C-CT
• rs34571703
• NM_001278.5:c.2209-208dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001278.5(CHUK):​c.2209-208dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 139,026 control chromosomes in the GnomAD database, including 848 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (848 hom., cov: 30)
• Consequence: CHUK NM_001278.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.274
• Publications: 0 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

ENSG00000236308 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-100189834-C-CT is Benign according to our data. Variant chr10-100189834-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1223963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 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.2209-208dupA		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.2209-327dupA		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.2208+1034dupA		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.2209-208_2209-207insA		intron	N/A	ENSP00000359424.6	O15111
	CHUK	ENST00000590930.5	TSL:1	n.3585-208_3585-207insA		intron	N/A
	CHUK	ENST00000896937.1		c.2203-208_2203-207insA		intron	N/A	ENSP00000566996.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 14436 AN: 139012 Hom.: 851 Cov.: 30

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0972

Gnomad NFE AF: 0.0684

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.104 AC: 14441 AN: 139026 Hom.: 848 Cov.: 30 AF XY: 0.106 AC XY: 7145 AN XY: 67142

African (AFR) AF: 0.170 AC: 6467 AN: 38026

American (AMR) AF: 0.0950 AC: 1328 AN: 13978

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 231 AN: 3312

East Asian (EAS) AF: 0.0945 AC: 455 AN: 4816

South Asian (SAS) AF: 0.0870 AC: 383 AN: 4402

European-Finnish (FIN) AF: 0.113 AC: 860 AN: 7608

Middle Eastern (MID) AF: 0.102 AC: 27 AN: 264

European-Non Finnish (NFE) AF: 0.0684 AC: 4366 AN: 63844

Other (OTH) AF: 0.103 AC: 195 AN: 1896

Alfa AF: 0.0128 Hom.: 9

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.27
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: rs34571703; hg19: chr10-101949591;