Variant 10-100189674-T-G 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.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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.84

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=-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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CHUK	NM_001278.5 linkuse as main transcript	c.2209-47A>C	intron_variant	ENST00000370397.8	NP_001269.3
CHUK	NM_001320928.2 linkuse as main transcript	c.*32-47A>C	intron_variant		NP_001307857.1
CHUK	XM_047424540.1 linkuse as main transcript	c.2208+1195A>C	intron_variant		XP_047280496.1
CHUK	XM_047424542.1 linkuse as main transcript	c.*31+1195A>C	intron_variant		XP_047280498.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
CHUK	ENST00000370397.8 linkuse as main transcript	c.2209-47A>C	intron_variant	1	NM_001278.5	ENSP00000359424	P1
CHUK	ENST00000590930.5 linkuse as main transcript	n.3585-47A>C	intron_variant, non_coding_transcript_variant	1
CHUK	ENST00000588656.1 linkuse as main transcript	n.240-47A>C	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7496

AN:

152162

Hom.:

516

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0243

AC:

6092

AN:

250922

Hom.:

305

AF XY:

0.0229

AC XY:

3107

AN XY:

135692

show subpopulations

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 SAS exome

AF:

0.0524

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.:

AF XY:

0.0134

AC XY:

8194

AN XY:

610244

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.0557

Gnomad4 SAS exome

AF:

0.0516

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00258

Gnomad4 OTH exome

AF:

0.0228

GnomAD4 genome

AF:

0.0496

AC:

7557

AN:

152280

Hom.:

534

Cov.:

AF XY:

0.0497

AC XY:

3698

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.0197

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.0592

Gnomad4 SAS

AF:

0.0533

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0284

Hom.:

Bravo

AF:

0.0557

Asia WGS

AF:

0.0640

AC:

221

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.046

DANN

Benign

0.37

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