chr16-88646828-A-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000101.4(CYBA):c.214T>C(p.Tyr72His) variant causes a missense change. The variant allele was found at a frequency of 0.672 in 1,612,206 control chromosomes in the GnomAD database, including 367,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.65 ( 32939 hom., cov: 32)
Exomes 𝑓: 0.67 ( 334674 hom. )
Consequence
CYBA
NM_000101.4 missense
NM_000101.4 missense
Scores
5
5
Clinical Significance
Conservation
PhyloP100: 4.22
Genes affected
CYBA (HGNC:2577): (cytochrome b-245 alpha chain) Cytochrome b is comprised of a light chain (alpha) and a heavy chain (beta). This gene encodes the light, alpha subunit which has been proposed as a primary component of the microbicidal oxidase system of phagocytes. Mutations in this gene are associated with autosomal recessive chronic granulomatous disease (CGD), that is characterized by the failure of activated phagocytes to generate superoxide, which is important for the microbicidal activity of these cells. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=1.2247359E-6).
BP6
?
Variant 16-88646828-A-G is Benign according to our data. Variant chr16-88646828-A-G is described in ClinVar as [Benign]. Clinvar id is 2263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88646828-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYBA | NM_000101.4 | c.214T>C | p.Tyr72His | missense_variant | 4/6 | ENST00000261623.8 | |
CYBA | XM_011522905.4 | c.214T>C | p.Tyr72His | missense_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYBA | ENST00000261623.8 | c.214T>C | p.Tyr72His | missense_variant | 4/6 | 1 | NM_000101.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.653 AC: 99158AN: 151878Hom.: 32915 Cov.: 32
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GnomAD3 exomes AF: 0.698 AC: 174863AN: 250626Hom.: 62429 AF XY: 0.690 AC XY: 93689AN XY: 135686
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GnomAD4 exome AF: 0.674 AC: 983701AN: 1460210Hom.: 334674 Cov.: 44 AF XY: 0.672 AC XY: 488360AN XY: 726538
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GnomAD4 genome ? AF: 0.653 AC: 99225AN: 151996Hom.: 32939 Cov.: 32 AF XY: 0.661 AC XY: 49133AN XY: 74292
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:11Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 16, 2021 | Variant summary: CYBA c.214T>C (p.Tyr72His) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.7 in 250626 control chromosomes, suggesting that it is the major allele and therefore benign. The observed variant frequency is approximately 1139 fold of the estimated maximal expected allele frequency for a pathogenic variant in CYBA causing Chronic Granulomatous Disease phenotype (0.00061), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.214T>C in individuals affected with Chronic Granulomatous Disease and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters have assessed the clinical significance of this variant after 2014: four have classified the variant as benign and one as likely pathogenic. Based on the evidence outlined above, the variant was classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 93% of patients studied by a panel of primary immunodeficiencies. Number of patients: 88. Only high quality variants are reported. - |
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
not provided Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 30709874, 17383305, 21884584, 18799874, 19689263, 11023926, 15078863, 23821607, 22396743, 23409188, 25095657, 23040216, 9445163, 24339896, 24392120, 29132304, 29454792) - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. - |
Very early onset inflammatory bowel disease Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Institute of Clinical Molecular Biology, Kiel University | Nov 06, 2018 | - - |
CYBA POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jul 01, 2009 | - - |
Chronic granulomatous disease Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 18, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T
MutationTaster
Benign
P;P;P
PROVEAN
Uncertain
D
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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