rs7909855

Variant names:

• chr10-100207455-C-G
• rs7909855
• NM_001278.5:c.1129-123G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-100207455-C-G
• chr10-100207455-C-T

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0690
• Publications: 10 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: 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=-0.9).
• BP6: Variant 10-100207455-C-G is Benign according to our data. Variant chr10-100207455-C-G is described in ClinVar as Benign. ClinVar VariationId 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.

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.1129-123G>C		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.1129-123G>C		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.1129-123G>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.1129-123G>C		intron	N/A	ENSP00000359424.6	O15111
	CHUK	ENST00000896937.1		c.1129-123G>C		intron	N/A	ENSP00000566996.1
	CHUK	ENST00000896938.1		c.1129-123G>C		intron	N/A	ENSP00000566997.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84052 AN: 151938 Hom.: 24159 Cov.: 33

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

African (AFR) AF: 0.717 AC: 10026 AN: 13982

American (AMR) AF: 0.409 AC: 10911 AN: 26670

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 6955 AN: 16284

East Asian (EAS) AF: 0.482 AC: 14910 AN: 30936

South Asian (SAS) AF: 0.340 AC: 18026 AN: 52964

European-Finnish (FIN) AF: 0.468 AC: 14743 AN: 31520

Middle Eastern (MID) AF: 0.465 AC: 1665 AN: 3580

European-Non Finnish (NFE) AF: 0.515 AC: 150914 AN: 293052

Other (OTH) AF: 0.510 AC: 14265 AN: 27974

GnomAD4 genome AF: 0.553 AC: 84137 AN: 152054 Hom.: 24194 Cov.: 33 AF XY: 0.548 AC XY: 40723 AN XY: 74334

African (AFR) AF: 0.718 AC: 29811 AN: 41498

American (AMR) AF: 0.460 AC: 7024 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2534 AN: 5168

South Asian (SAS) AF: 0.350 AC: 1690 AN: 4828

European-Finnish (FIN) AF: 0.466 AC: 4917 AN: 10558

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34796 AN: 67940

Other (OTH) AF: 0.538 AC: 1138 AN: 2116

Alfa AF: 0.527 Hom.: 2550

Bravo AF: 0.560

Asia WGS AF: 0.461 AC: 1604 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	-0.90
CADD	Benign	6.5
DANN	Benign	0.67
PhyloP100		0.069
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: rs7909855; hg19: chr10-101967212;