chr10-100193568-A-G

Variant names:

• chr10-100193568-A-G
• rs55679482
• NM_001278.5:c.1975-137T>C

Variant summary

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

The NM_001278.5(CHUK):​c.1975-137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,026,538 control chromosomes in the GnomAD database, including 930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (601 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (329 hom.)
• Consequence: CHUK NM_001278.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0500
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• cocoon syndrome

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-100193568-A-G is Benign according to our data. Variant chr10-100193568-A-G is described in ClinVar as Benign. ClinVar VariationId is 1261441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278.5. 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	NM_001278.5	MANE Select	c.1975-137T>C		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.1975-137T>C		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.1975-137T>C		intron	N/A	NP_001427992.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHUK	ENST00000370397.8	TSL:1 MANE Select	c.1975-137T>C		intron	N/A	ENSP00000359424.6	O15111
	CHUK	ENST00000590930.5	TSL:1	n.2375T>C		non_coding_transcript_exon	Exon 1 of 3
	CHUK	ENST00000896937.1		c.1975-143T>C		intron	N/A	ENSP00000566996.1

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7429 AN: 152154 Hom.: 600 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.00545 AC: 4769 AN: 874266 Hom.: 329 Cov.: 11 AF XY: 0.00465 AC XY: 2105 AN XY: 452874

African (AFR) AF: 0.168 AC: 3653 AN: 21754

American (AMR) AF: 0.00944 AC: 336 AN: 35596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21648

East Asian (EAS) AF: 0.00 AC: 0 AN: 34046

South Asian (SAS) AF: 0.000232 AC: 16 AN: 68862

European-Finnish (FIN) AF: 0.000112 AC: 4 AN: 35864

Middle Eastern (MID) AF: 0.00583 AC: 20 AN: 3428

European-Non Finnish (NFE) AF: 0.000471 AC: 288 AN: 612110

Other (OTH) AF: 0.0110 AC: 452 AN: 40958

GnomAD4 genome AF: 0.0488 AC: 7435 AN: 152272 Hom.: 601 Cov.: 32 AF XY: 0.0466 AC XY: 3473 AN XY: 74454

African (AFR) AF: 0.169 AC: 7014 AN: 41536

American (AMR) AF: 0.0181 AC: 277 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68024

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0460 Hom.: 66

Bravo AF: 0.0556

Asia WGS AF: 0.00808 AC: 29 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.86
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55679482; hg19: chr10-101953325;