rs11597086

chr10-100193948-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001278.5(CHUK):c.1974+36T>G variant causes a intron 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 NM_001278.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.660

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
CHUK	NM_001278.5	c.1974+36T>G		intron_variant		ENST00000370397.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHUK	ENST00000370397.8	c.1974+36T>G		intron_variant		1	NM_001278.5	P1
CHUK	ENST00000590930.5	n.1995T>G		non_coding_transcript_exon_variant	1/3	1
CHUK	ENST00000588656.1	n.96+36T>G		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.301 AC: 74851 AN: 248932 Hom.: 13660 AF XY: 0.305 AC XY: 41199 AN XY: 134924

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 SAS exome AF: 0.153

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

Gnomad4 AFR exome AF: 0.0692

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.0506

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.351

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

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.0643

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.309

Alfa AF: 0.386 Hom.: 13087

Bravo AF: 0.278

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.6
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs11597086; hg19: chr10-101953705; COSMIC: COSV64918161; COSMIC: COSV64918161;