10-100189834-CTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr10-100189834-C-CTTTTTTTTTTT
• rs34571703
• NM_001278.5:c.2209-218_2209-208dupAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001278.5(CHUK):​c.2209-218_2209-208dupAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 139,118 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000014 (0 hom., cov: 30)
• Consequence: CHUK NM_001278.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.2209-218_2209-208dupAAAAAAAAAAA		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.2209-337_2209-327dupAAAAAAAAAAA		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.2208+1024_2208+1034dupAAAAAAAAAAA		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_2209-207insAAAAAAAAAAA		intron	N/A	ENSP00000359424.6	O15111
	CHUK	ENST00000590930.5	TSL:1	n.3585-208_3585-207insAAAAAAAAAAA		intron	N/A
	CHUK	ENST00000896937.1		c.2203-208_2203-207insAAAAAAAAAAA		intron	N/A	ENSP00000566996.1

Frequencies

GnomAD3 genomes AF: 0.0000144 AC: 2 AN: 139118 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000716

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000144 AC: 2 AN: 139118 Hom.: 0 Cov.: 30 AF XY: 0.0000298 AC XY: 2 AN XY: 67174

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000263 AC: 1 AN: 37994

American (AMR) AF: 0.0000716 AC: 1 AN: 13976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3312

East Asian (EAS) AF: 0.00 AC: 0 AN: 4832

South Asian (SAS) AF: 0.00 AC: 0 AN: 4424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63908

Other (OTH) AF: 0.00 AC: 0 AN: 1888

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34571703; hg19: chr10-101949591;