chr10-100229753-C-T

Variant names:

• chr10-100229753-C-T
• rs12770784
• ENST00000751302.1:n.90C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000751302.1(CHUK-DT):​n.90C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 576,216 control chromosomes in the GnomAD database, including 1,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (583 hom., cov: 32)
  • Exomes 𝑓: 0.054 (775 hom.)
• Consequence: CHUK-DT ENST00000751302.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.777
• Publications: 7 publications found

Genes affected

CHUK-DT (HGNC:55813): (CHUK divergent transcript)

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 Gene-Disease associations (from GenCC):

• cocoon syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Bartsocas-Papas syndrome 2

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-100229753-C-T is Benign according to our data. Variant chr10-100229753-C-T is described in ClinVar as Benign. ClinVar VariationId is 1181190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000751302.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHUK-DT	NR_186418.1		n.65+29C>T		intron	N/A
	CHUK-DT	NR_186419.1		n.65+29C>T		intron	N/A
	CHUK	NM_001278.5	MANE Select	c.-221G>A		upstream_gene	N/A	NP_001269.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHUK-DT	ENST00000751302.1		n.90C>T		non_coding_transcript_exon	Exon 1 of 1
	CHUK-DT	ENST00000444359.1	TSL:5	n.58+29C>T		intron	N/A
	CHUK-DT	ENST00000667469.2		n.96+29C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11410 AN: 152136 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0731

GnomAD4 exome AF: 0.0536 AC: 22741 AN: 423962 Hom.: 775 Cov.: 0 AF XY: 0.0533 AC XY: 11916 AN XY: 223538

African (AFR) AF: 0.144 AC: 1637 AN: 11386

American (AMR) AF: 0.0496 AC: 859 AN: 17336

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 688 AN: 12838

East Asian (EAS) AF: 0.0686 AC: 2021 AN: 29444

South Asian (SAS) AF: 0.0590 AC: 2577 AN: 43682

European-Finnish (FIN) AF: 0.0535 AC: 1512 AN: 28282

Middle Eastern (MID) AF: 0.0557 AC: 103 AN: 1848

European-Non Finnish (NFE) AF: 0.0464 AC: 11813 AN: 254556

Other (OTH) AF: 0.0623 AC: 1531 AN: 24590

GnomAD4 genome AF: 0.0750 AC: 11422 AN: 152254 Hom.: 583 Cov.: 32 AF XY: 0.0745 AC XY: 5549 AN XY: 74436

African (AFR) AF: 0.139 AC: 5789 AN: 41534

American (AMR) AF: 0.0526 AC: 804 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.0559 AC: 290 AN: 5186

South Asian (SAS) AF: 0.0645 AC: 311 AN: 4824

European-Finnish (FIN) AF: 0.0555 AC: 589 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3208 AN: 68018

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0536 Hom.: 396

Bravo AF: 0.0771

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.1
DANN	Benign	0.79
PhyloP100		-0.78
PromoterAI		-0.076	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12770784; hg19: chr10-101989510;