Genetic Variant CHUK:c.1129-123G>C (chr10-100207455-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001278.5(CHUK):c.1129-123G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 649,016 control chromosomes in the GnomAD database, including 84,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 24194 hom., cov: 33)

Exomes 𝑓: 0.49 ( 60220 hom. )

Consequence

CHUK
NM_001278.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0690

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=-0.9).

BP6

Variant 10-100207455-C-G is Benign according to our data. Variant chr10-100207455-C-G is described in ClinVar as [Benign]. Clinvar id is 1289583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHUK	NM_001278.5 link	c.1129-123G>C		intron_variant	Intron 10 of 20	ENST00000370397.8	NP_001269.3	O15111

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHUK	ENST00000370397.8 link	c.1129-123G>C		intron_variant	Intron 10 of 20	1	NM_001278.5	ENSP00000359424.6		O15111

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

84052

AN:

151938

Hom.:

24159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.718

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.466

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.534

GnomAD4 exome

AF:

0.488

AC:

242415

AN:

496962

Hom.:

60220

AF XY:

0.480

AC XY:

128845

AN XY:

268466

show subpopulations

Gnomad4 AFR exome

AF:

0.717

Gnomad4 AMR exome

AF:

0.409

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.482

Gnomad4 SAS exome

AF:

0.340

Gnomad4 FIN exome

AF:

0.468

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.510

GnomAD4 genome

AF:

0.553

AC:

84137

AN:

152054

Hom.:

24194

Cov.:

AF XY:

0.548

AC XY:

40723

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.718

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.431

Gnomad4 EAS

AF:

0.490

Gnomad4 SAS

AF:

0.350

Gnomad4 FIN

AF:

0.466

Gnomad4 NFE

AF:

0.512

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.527

Hom.:

2550

Bravo

AF:

0.560

Asia WGS

AF:

0.461

AC:

1604

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.5

DANN

Benign

0.67

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