rs767148046
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5
The NM_000101.4(CYBA):c.166C>T(p.Arg56Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,611,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R56G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000101.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYBA | NM_000101.4 | c.166C>T | p.Arg56Trp | missense_variant | 3/6 | ENST00000261623.8 | |
CYBA | XM_011522905.4 | c.166C>T | p.Arg56Trp | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYBA | ENST00000261623.8 | c.166C>T | p.Arg56Trp | missense_variant | 3/6 | 1 | NM_000101.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000285 AC: 7AN: 245838Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133578
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1458888Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 725772
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
Chronic granulomatous disease Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces arginine with tryptophan at codon 56 of the CYBA protein (p.Arg56Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs767148046, ExAC 0.009%). 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