chr16-88643400-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000101.4(CYBA):c.541G>C(p.Gly181Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G181G) has been classified as Likely benign.
Frequency
Consequence
NM_000101.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYBA | NM_000101.4 | c.541G>C | p.Gly181Arg | missense_variant | 6/6 | ENST00000261623.8 | |
CYBA | XM_011522905.4 | c.*1766G>C | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYBA | ENST00000261623.8 | c.541G>C | p.Gly181Arg | missense_variant | 6/6 | 1 | NM_000101.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74278
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2023 | The c.541G>C (p.G181R) alteration is located in exon 6 (coding exon 6) of the CYBA gene. This alteration results from a G to C substitution at nucleotide position 541, causing the glycine (G) at amino acid position 181 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | This sequence change replaces glycine with arginine at codon 181 of the CYBA protein (p.Gly181Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with CYBA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at