Variant chr10-100193518-C-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.1975-87G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 1,483,672 control chromosomes in the GnomAD database, including 2,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 127 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1878 hom. )

Consequence

CHUK
NM_001278.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.876

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=-0.82).

BP6

Variant 10-100193518-C-G is Benign according to our data. Variant chr10-100193518-C-G is described in ClinVar as [Benign]. Clinvar id is 1238295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0554 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.1975-87G>C		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.1975-87G>C	intron_variant		1	NM_001278.5	ENSP00000359424	P1
CHUK	ENST00000590930.5 linkuse as main transcript	n.2425G>C	non_coding_transcript_exon_variant	1/3	1
CHUK	ENST00000588656.1 linkuse as main transcript	n.97-87G>C	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

5194

AN:

152188

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00943

Gnomad AMI

AF:

0.0826

Gnomad AMR

AF:

0.0293

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.0241

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0569

Gnomad OTH

AF:

0.0224

GnomAD4 exome

AF:

0.0486

AC:

64730

AN:

1331366

Hom.:

1878

Cov.:

AF XY:

0.0471

AC XY:

31539

AN XY:

669120

show subpopulations

Gnomad4 AFR exome

AF:

0.00794

Gnomad4 AMR exome

AF:

0.0150

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.0000771

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.0296

Gnomad4 NFE exome

AF:

0.0587

Gnomad4 OTH exome

AF:

0.0407

GnomAD4 genome

AF:

0.0341

AC:

5193

AN:

152306

Hom.:

127

Cov.:

AF XY:

0.0322

AC XY:

2395

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00941

Gnomad4 AMR

AF:

0.0292

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00890

Gnomad4 FIN

AF:

0.0241

Gnomad4 NFE

AF:

0.0569

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0252

Hom.:

Bravo

AF:

0.0325

Asia WGS

AF:

0.00664

AC:

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	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.92

DANN

Benign

0.56

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

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