rs1804006

Variant names:

• chr16-88648088-T-C
• rs1804006
• NM_000101.4:c.85A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000101.4(CYBA):​c.85A>G​(p.Thr29Ala) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYBA NM_000101.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12
• Publications: 2 publications found

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: Labcorp Genetics (formerly Invitae), G2P
• chronic granulomatous disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37338072).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000101.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	NM_000101.4	MANE Select	c.85A>G	p.Thr29Ala	missense	Exon 2 of 6	NP_000092.2	P13498

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	ENST00000261623.8	TSL:1 MANE Select	c.85A>G	p.Thr29Ala	missense	Exon 2 of 6	ENSP00000261623.3	P13498
	CYBA	ENST00000569359.5	TSL:1	c.85A>G	p.Thr29Ala	missense	Exon 2 of 5	ENSP00000456079.1	H3BR52
	CYBA	ENST00000696161.1		c.85A>G	p.Thr29Ala	missense	Exon 2 of 6	ENSP00000512451.1	A0A8Q3WL26

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.66	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.37	T
PhyloP100		3.1
PROVEAN	Uncertain	-2.7	D
MVP		0.42
ClinPred		0.85	D
GERP RS		4.0
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.084

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1804006; hg19: chr16-88714496;