Variant chr10-100193524-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001278.5(CHUK):c.1975-93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 1,420,470 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 77 hom., cov: 32)

Exomes 𝑓: 0.020 ( 386 hom. )

Consequence

CHUK
NM_001278.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.82

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=-0.91).

BP6

Variant 10-100193524-C-T is Benign according to our data. Variant chr10-100193524-C-T is described in ClinVar as [Benign]. Clinvar id is 1178394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0267 (4062/152254) while in subpopulation AMR AF= 0.0421 (644/15298). AF 95% confidence interval is 0.0394. There are 77 homozygotes in gnomad4. There are 2298 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 77 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHUK	NM_001278.5 linkuse as main transcript	c.1975-93G>A		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.1975-93G>A	intron_variant		1	NM_001278.5	ENSP00000359424	P1
CHUK	ENST00000590930.5 linkuse as main transcript	n.2419G>A	non_coding_transcript_exon_variant	1/3	1
CHUK	ENST00000588656.1 linkuse as main transcript	n.97-93G>A	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4066

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0420

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0362

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.0746

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0234

GnomAD4 exome

AF:

0.0200

AC:

25417

AN:

1268216

Hom.:

386

Cov.:

AF XY:

0.0201

AC XY:

12875

AN XY:

640176

show subpopulations

Gnomad4 AFR exome

AF:

0.0244

Gnomad4 AMR exome

AF:

0.0512

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.0423

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.0687

Gnomad4 NFE exome

AF:

0.0151

Gnomad4 OTH exome

AF:

0.0212

GnomAD4 genome

AF:

0.0267

AC:

4062

AN:

152254

Hom.:

Cov.:

AF XY:

0.0309

AC XY:

2298

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0230

Gnomad4 AMR

AF:

0.0421

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.0363

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.0746

Gnomad4 NFE

AF:

0.0180

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0237

Hom.:

Bravo

AF:

0.0244

Asia WGS

AF:

0.0340

AC:

118

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

-0.91

CADD

Benign

0.032

DANN

Benign

0.40

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