chrX-37782132-CCG-GGT

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1PP5

The NM_000397.4(CYBB):​c.90_92delCCGinsGGT​(p.TyrArg30*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 23)

Consequence

CYBB
NM_000397.4 stop_gained

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.49

Publications

3 publications found
Variant links:
Genes affected
CYBB (HGNC:2578): (cytochrome b-245 beta chain) Cytochrome b (-245) is composed of cytochrome b alpha (CYBA) and beta (CYBB) chain. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes. CYBB deficiency is one of five described biochemical defects associated with chronic granulomatous disease (CGD). In this disorder, there is decreased activity of phagocyte NADPH oxidase; neutrophils are able to phagocytize bacteria but cannot kill them in the phagocytic vacuoles. The cause of the killing defect is an inability to increase the cell's respiration and consequent failure to deliver activated oxygen into the phagocytic vacuole. [provided by RefSeq, Jul 2008]
CYBB Gene-Disease associations (from GenCC):
  • granulomatous disease, chronic, X-linked
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • chronic granulomatous disease
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency
    Inheritance: XL, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 144 pathogenic variants in the truncated region.
PP5
Variant X-37782132-CCG-GGT is Pathogenic according to our data. Variant chrX-37782132-CCG-GGT is described in CliVar as Pathogenic. Clinvar id is 10940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-37782132-CCG-GGT is described in CliVar as Pathogenic. Clinvar id is 10940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-37782132-CCG-GGT is described in CliVar as Pathogenic. Clinvar id is 10940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-37782132-CCG-GGT is described in CliVar as Pathogenic. Clinvar id is 10940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-37782132-CCG-GGT is described in CliVar as Pathogenic. Clinvar id is 10940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-37782132-CCG-GGT is described in CliVar as Pathogenic. Clinvar id is 10940.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYBBNM_000397.4 linkc.90_92delCCGinsGGT p.TyrArg30* stop_gained ENST00000378588.5 NP_000388.2 P04839A0A0S2Z3S6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYBBENST00000378588.5 linkc.90_92delCCGinsGGT p.TyrArg30* stop_gained 1 NM_000397.4 ENSP00000367851.4 P04839
ENSG00000250349ENST00000465127.1 linkc.171+356132_171+356134delCCGinsGGT intron_variant Intron 3 of 8 5 ENSP00000417050.1 B4E171

Frequencies

GnomAD3 genomes
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Granulomatous disease, chronic, X-linked Pathogenic:1
Jan 01, 2005
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.5
Mutation Taster
=1/199
disease causing (fs/PTC)

Splicing

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

Publications

Other links and lift over

dbSNP: rs387906486; hg19: chrX-37641385; API