NM_000397.4(CYBB):c.45+1G>T AND Granulomatous disease, chronic, X-linked

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 2, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003509044.1

Allele description [Variation Report for NM_000397.4(CYBB):c.45+1G>T]

NM_000397.4(CYBB):c.45+1G>T

Genes:

LOC130068093:ATAC-STARR-seq lymphoblastoid active region 29519 [Gene]
CYBB:cytochrome b-245 beta chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_000397.4(CYBB):c.45+1G>T

HGVS:

NC_000023.11:g.37780123G>T
NG_009065.1:g.5107G>T
NG_202508.1:g.123G>T
NM_000397.4:c.45+1G>TMANE SELECT
LRG_53:g.5107G>T
NC_000023.10:g.37639376G>T

Molecular consequence:

NM_000397.4:c.45+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Granulomatous disease, chronic, X-linked
Synonyms:: CYTOCHROME b-NEGATIVE GRANULOMATOUS DISEASE, CHRONIC, X-LINKED; GRANULOMATOUS DISEASE, CHRONIC, X-LINKED, SOMATIC MOSAIC
Identifiers:: MONDO: MONDO:0010600; MedGen: C1844376; Orphanet: 379; OMIM: 306400

Recent activity

Clear Turn Off Turn On

Taxonomy Links for Nucleotide (Select 2462583895) (1)
Taxonomy

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004298945	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 2, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 20228266, 29560547, 35140711, 16199547, 9585602, 20729109, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004298945

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 2, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Rapid genetic analysis of x-linked chronic granulomatous disease by high-resolution melting.

Hill HR, Augustine NH, Pryor RJ, Reed GH, Bagnato JD, Tebo AE, Bender JM, Pasi BM, Chinen J, Hanson IC, de Boer M, Roos D, Wittwer CT.

J Mol Diagn. 2010 May;12(3):368-76. doi: 10.2353/jmoldx.2010.090147. Epub 2010 Mar 12.

PubMed [citation]

PMID:: 20228266
PMCID:: PMC2860474

A Cohort of 169 Chronic Granulomatous Disease Patients Exposed to BCG Vaccination: a Retrospective Study from a Single Center in Shanghai, China (2004-2017).

Zhou Q, Hui X, Ying W, Hou J, Wang W, Liu D, Wang Y, Yu Y, Wang J, Sun J, Zhang Q, Wang X.

J Clin Immunol. 2018 Apr;38(3):260-272. doi: 10.1007/s10875-018-0486-y. Epub 2018 Mar 20.

PubMed [citation]

PMID:: 29560547

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV004298945.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individuals with chronic granulomatous disease (PMID: 20228266, 20729109, 29560547, 35140711). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 1 of the CYBB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CYBB are known to be pathogenic (PMID: 9585602, 20729109).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

ClinVar

Relating variation to medicine