rs11597086

Variant names:

• chr10-100193948-A-C
• rs11597086
• ENST00000590930.5:n.1995T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-100193948-A-C
• chr10-100193948-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000590930.5(CHUK):​n.1995T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,576,486 control chromosomes in the GnomAD database, including 122,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (8043 hom., cov: 32)
  • Exomes 𝑓: 0.38 (114027 hom.)
• Consequence: CHUK ENST00000590930.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.660
• Publications: 58 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, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• Bartsocas-Papas syndrome 2

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-100193948-A-C is Benign according to our data. Variant chr10-100193948-A-C is described in ClinVar as Benign. ClinVar VariationId is 1235205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHUK	NM_001278.5	c.1974+36T>G		intron_variant	Intron 18 of 20	ENST00000370397.8	NP_001269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHUK	ENST00000590930.5	n.1995T>G		non_coding_transcript_exon_variant	Exon 1 of 3	1
CHUK	ENST00000370397.8	c.1974+36T>G		intron_variant	Intron 18 of 20	1	NM_001278.5	ENSP00000359424.6
CHUK	ENST00000588656.1	n.96+36T>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44033 AN: 152046 Hom.: 8045 Cov.: 32

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.308

GnomAD2 exomes AF: 0.301 AC: 74851 AN: 248932 AF XY: 0.305

Gnomad AFR exome AF: 0.0778

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.312

Gnomad EAS exome AF: 0.0603

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.340

GnomAD4 exome AF: 0.384 AC: 546337 AN: 1424322 Hom.: 114027 Cov.: 25 AF XY: 0.379 AC XY: 269284 AN XY: 711008

African (AFR) AF: 0.0692 AC: 2284 AN: 32982

American (AMR) AF: 0.233 AC: 10388 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 7986 AN: 25902

East Asian (EAS) AF: 0.0506 AC: 2001 AN: 39554

South Asian (SAS) AF: 0.158 AC: 13506 AN: 85696

European-Finnish (FIN) AF: 0.331 AC: 17183 AN: 51966

Middle Eastern (MID) AF: 0.267 AC: 1506 AN: 5648

European-Non Finnish (NFE) AF: 0.436 AC: 470721 AN: 1078714

Other (OTH) AF: 0.351 AC: 20762 AN: 59222

GnomAD4 genome AF: 0.289 AC: 44022 AN: 152164 Hom.: 8043 Cov.: 32 AF XY: 0.282 AC XY: 21002 AN XY: 74380

African (AFR) AF: 0.0884 AC: 3674 AN: 41542

American (AMR) AF: 0.298 AC: 4552 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1083 AN: 3468

East Asian (EAS) AF: 0.0643 AC: 333 AN: 5182

South Asian (SAS) AF: 0.157 AC: 756 AN: 4826

European-Finnish (FIN) AF: 0.325 AC: 3442 AN: 10592

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29083 AN: 67964

Other (OTH) AF: 0.309 AC: 653 AN: 2114

Alfa AF: 0.374 Hom.: 16015

Bravo AF: 0.278

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 47. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.74
PhyloP100		0.66
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: rs11597086; hg19: chr10-101953705; COSMIC: COSV64918161; COSMIC: COSV64918161;