rs2274174

Variant names:

• chr10-100193524-C-T
• rs2274174
• NM_001278.5:c.1975-93G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001278.5(CHUK):​c.1975-93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 1,420,470 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (77 hom., cov: 32)
  • Exomes 𝑓: 0.020 (386 hom.)
• Consequence: CHUK NM_001278.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.82
• Publications: 1 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=-0.91).
• BP6: Variant 10-100193524-C-T is Benign according to our data. Variant chr10-100193524-C-T is described in ClinVar as Benign. ClinVar VariationId is 1178394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0267 (4062/152254) while in subpopulation AMR AF = 0.0421 (644/15298). AF 95% confidence interval is 0.0394. There are 77 homozygotes in GnomAd4. There are 2298 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 77 AR gene

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.1975-93G>A		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.1975-93G>A		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.1975-93G>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.1975-93G>A		intron	N/A	ENSP00000359424.6	O15111
	CHUK	ENST00000590930.5	TSL:1	n.2419G>A		non_coding_transcript_exon	Exon 1 of 3
	CHUK	ENST00000896937.1		c.1975-99G>A		intron	N/A	ENSP00000566996.1

Frequencies

GnomAD3 genomes AF: 0.0267 AC: 4066 AN: 152136 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0362

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.0200 AC: 25417 AN: 1268216 Hom.: 386 Cov.: 18 AF XY: 0.0201 AC XY: 12875 AN XY: 640176

African (AFR) AF: 0.0244 AC: 731 AN: 29904

American (AMR) AF: 0.0512 AC: 2185 AN: 42712

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 265 AN: 24740

East Asian (EAS) AF: 0.0423 AC: 1626 AN: 38462

South Asian (SAS) AF: 0.0219 AC: 1787 AN: 81462

European-Finnish (FIN) AF: 0.0687 AC: 3135 AN: 45648

Middle Eastern (MID) AF: 0.0490 AC: 255 AN: 5206

European-Non Finnish (NFE) AF: 0.0151 AC: 14288 AN: 946158

Other (OTH) AF: 0.0212 AC: 1145 AN: 53924

GnomAD4 genome AF: 0.0267 AC: 4062 AN: 152254 Hom.: 77 Cov.: 32 AF XY: 0.0309 AC XY: 2298 AN XY: 74436

African (AFR) AF: 0.0230 AC: 956 AN: 41556

American (AMR) AF: 0.0421 AC: 644 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3468

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5180

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4832

European-Finnish (FIN) AF: 0.0746 AC: 790 AN: 10586

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1221 AN: 68014

Other (OTH) AF: 0.0237 AC: 50 AN: 2114

Alfa AF: 0.0225 Hom.: 17

Bravo AF: 0.0244

Asia WGS AF: 0.0340 AC: 118 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	-0.91
CADD	Benign	0.032
DANN	Benign	0.40
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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: rs2274174; hg19: chr10-101953281;