Variant chr10-100193948-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.660

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
CHUK	NM_001278.5 linkuse as main transcript	c.1974+36T>G		intron_variant		ENST00000370397.8	NP_001269.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
CHUK	ENST00000370397.8 linkuse as main transcript	c.1974+36T>G	intron_variant		1	NM_001278.5	ENSP00000359424	P1
CHUK	ENST00000590930.5 linkuse as main transcript	n.1995T>G	non_coding_transcript_exon_variant	1/3	1
CHUK	ENST00000588656.1 linkuse as main transcript	n.96+36T>G	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44033

AN:

152046

Hom.:

8045

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.379

AC XY:

269284

AN XY:

711008

show subpopulations

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.:

AF XY:

0.282

AC XY:

21002

AN XY:

74380

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

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. -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over