X-37780083-G-C
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_000397.4(CYBB):āc.6G>Cā(p.Gly2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,208,330 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.00022 ( 0 hom., 5 hem., cov: 22)
Exomes š: 0.000013 ( 0 hom. 3 hem. )
Consequence
CYBB
NM_000397.4 synonymous
NM_000397.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.625
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant X-37780083-G-C is Benign according to our data. Variant chrX-37780083-G-C is described in ClinVar as [Benign]. Clinvar id is 788249.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.625 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000215 (24/111572) while in subpopulation AFR AF= 0.000685 (21/30674). AF 95% confidence interval is 0.000458. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 5 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYBB | NM_000397.4 | c.6G>C | p.Gly2= | synonymous_variant | 1/13 | ENST00000378588.5 | NP_000388.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYBB | ENST00000378588.5 | c.6G>C | p.Gly2= | synonymous_variant | 1/13 | 1 | NM_000397.4 | ENSP00000367851 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000215 AC: 24AN: 111572Hom.: 0 Cov.: 22 AF XY: 0.000148 AC XY: 5AN XY: 33764
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GnomAD3 exomes AF: 0.0000328 AC: 6AN: 183148Hom.: 0 AF XY: 0.0000296 AC XY: 2AN XY: 67658
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GnomAD4 exome AF: 0.0000128 AC: 14AN: 1096758Hom.: 0 Cov.: 28 AF XY: 0.00000828 AC XY: 3AN XY: 362182
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GnomAD4 genome AF: 0.000215 AC: 24AN: 111572Hom.: 0 Cov.: 22 AF XY: 0.000148 AC XY: 5AN XY: 33764
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Granulomatous disease, chronic, X-linked Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 11, 2024 | - - |
Chronic granulomatous disease Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 16, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at