chr10-100219496-T-C

Position:

• chr10-100219496-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001278.5(CHUK):​c.475-137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 641,502 control chromosomes in the GnomAD database, including 1,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.076 (787 hom., cov: 32)
  • Exomes 𝑓: 0.041 (774 hom.)
• Consequence: CHUK NM_001278.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.44

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 10-100219496-T-C is Benign according to our data. Variant chr10-100219496-T-C is described in ClinVar as [Benign]. Clinvar id is 1288291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHUK	NM_001278.5	c.475-137A>G		intron_variant		ENST00000370397.8	NP_001269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHUK	ENST00000370397.8	c.475-137A>G		intron_variant		1	NM_001278.5	ENSP00000359424.6

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11543 AN: 152054 Hom.: 771 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0711

GnomAD4 exome AF: 0.0415 AC: 20285 AN: 489330 Hom.: 774 AF XY: 0.0417 AC XY: 10939 AN XY: 262474

Gnomad4 AFR exome AF: 0.181

Gnomad4 AMR exome AF: 0.0654

Gnomad4 ASJ exome AF: 0.0212

Gnomad4 EAS exome AF: 0.0963

Gnomad4 SAS exome AF: 0.0704

Gnomad4 FIN exome AF: 0.0674

Gnomad4 NFE exome AF: 0.0197

Gnomad4 OTH exome AF: 0.0465

GnomAD4 genome AF: 0.0762 AC: 11599 AN: 152172 Hom.: 787 Cov.: 32 AF XY: 0.0804 AC XY: 5980 AN XY: 74418

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0617

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.0959

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.0207

Gnomad4 OTH AF: 0.0703

Alfa AF: 0.0543 Hom.: 96

Bravo AF: 0.0801

Asia WGS AF: 0.0970 AC: 335 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.94
CADD	Benign	0.20
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs17112751; hg19: chr10-101979253; COSMIC: COSV64917499;