16-88643380-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000101.4(CYBA):​c.561C>G​(p.Pro187Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. P187P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

CYBA
NM_000101.4 synonymous

Scores

2

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.552

Publications

0 publications found
Variant links:
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]
CYBA Gene-Disease associations (from GenCC):
  • granulomatous disease, chronic, autosomal recessive, cytochrome b-negative
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • chronic granulomatous disease
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP7
Synonymous conserved (PhyloP=-0.552 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYBANM_000101.4 linkc.561C>G p.Pro187Pro synonymous_variant Exon 6 of 6 ENST00000261623.8 NP_000092.2 P13498B4DT46
CYBAXM_011522905.4 linkc.*1786C>G 3_prime_UTR_variant Exon 6 of 6 XP_011521207.1 H3BNP7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYBAENST00000261623.8 linkc.561C>G p.Pro187Pro synonymous_variant Exon 6 of 6 1 NM_000101.4 ENSP00000261623.3 P13498

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Chronic granulomatous disease Uncertain:1
Feb 19, 2025
Natera, Inc.
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.79
DANN
Benign
0.49
PhyloP100
-0.55
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

hg19: chr16-88709788; API