NM_001278.5:c.2209-47A>C

Variant names:

• chr10-100189674-T-G
• rs17880060
• NM_001278.5:c.2209-47A>C

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.2209-47A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,353,546 control chromosomes in the GnomAD database, including 1,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (534 hom., cov: 32)
  • Exomes 𝑓: 0.013 (661 hom.)
• Consequence: CHUK NM_001278.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.84
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet
• Bartsocas-Papas syndrome 2

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 10-100189674-T-G is Benign according to our data. Variant chr10-100189674-T-G is described in ClinVar as Benign. ClinVar VariationId is 1262254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 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.2209-47A>C		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.2209-166A>C		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.2208+1195A>C		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.2209-47A>C		intron	N/A	ENSP00000359424.6	O15111
	CHUK	ENST00000590930.5	TSL:1	n.3585-47A>C		intron	N/A
	CHUK	ENST00000896937.1		c.2203-47A>C		intron	N/A	ENSP00000566996.1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7496 AN: 152162 Hom.: 516 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.0478

GnomAD2 exomes AF: 0.0243 AC: 6092 AN: 250922 AF XY: 0.0229

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.0116

Gnomad ASJ exome AF: 0.00814

Gnomad EAS exome AF: 0.0600

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00266

Gnomad OTH exome AF: 0.0163

GnomAD4 exome AF: 0.0129 AC: 15470 AN: 1201266 Hom.: 661 Cov.: 18 AF XY: 0.0134 AC XY: 8194 AN XY: 610244

African (AFR) AF: 0.165 AC: 4764 AN: 28860

American (AMR) AF: 0.0130 AC: 578 AN: 44416

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 249 AN: 24598

East Asian (EAS) AF: 0.0557 AC: 2142 AN: 38484

South Asian (SAS) AF: 0.0516 AC: 4186 AN: 81132

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53282

Middle Eastern (MID) AF: 0.0199 AC: 105 AN: 5272

European-Non Finnish (NFE) AF: 0.00258 AC: 2251 AN: 873382

Other (OTH) AF: 0.0228 AC: 1183 AN: 51840

GnomAD4 genome AF: 0.0496 AC: 7557 AN: 152280 Hom.: 534 Cov.: 32 AF XY: 0.0497 AC XY: 3698 AN XY: 74480

African (AFR) AF: 0.153 AC: 6361 AN: 41542

American (AMR) AF: 0.0197 AC: 302 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.0592 AC: 307 AN: 5188

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00275 AC: 187 AN: 68006

Other (OTH) AF: 0.0473 AC: 100 AN: 2116

Alfa AF: 0.0316 Hom.: 67

Bravo AF: 0.0557

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.046
DANN	Benign	0.37
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17880060; hg19: chr10-101949431; COSMIC: COSV64917286; COSMIC: COSV64917286;