10-100207455-C-T

Variant names:

• chr10-100207455-C-T
• rs7909855
• NM_001278.5:c.1129-123G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001278.5(CHUK):​c.1129-123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHUK NM_001278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.1129-123G>A		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.1129-123G>A		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.1129-123G>A		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.1129-123G>A		intron	N/A	ENSP00000359424.6	O15111
	CHUK	ENST00000896937.1		c.1129-123G>A		intron	N/A	ENSP00000566996.1
	CHUK	ENST00000896938.1		c.1129-123G>A		intron	N/A	ENSP00000566997.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 497590 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 268772

African (AFR) AF: 0.00 AC: 0 AN: 13986

American (AMR) AF: 0.00 AC: 0 AN: 26688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16318

East Asian (EAS) AF: 0.00 AC: 0 AN: 30982

South Asian (SAS) AF: 0.00 AC: 0 AN: 52984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 293460

Other (OTH) AF: 0.00 AC: 0 AN: 28024

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.4
DANN	Benign	0.85
PhyloP100		0.069

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: rs7909855; hg19: chr10-101967212;