16-88651007-G-C

Variant names:

• chr16-88651007-G-C
• NM_000101.4:c.7C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000101.4(CYBA):​c.7C>G​(p.Gln3Glu) 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: 35)
• Consequence: CYBA NM_000101.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36210728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4	c.7C>G	p.Gln3Glu	missense_variant	Exon 1 of 6	ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.7C>G	p.Gln3Glu	missense_variant	Exon 1 of 6		XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8	c.7C>G	p.Gln3Glu	missense_variant	Exon 1 of 6	1	NM_000101.4	ENSP00000261623.3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	T;T;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.21	T;T;T;T
Sift4G	Benign	0.072	T;D;T;.
Polyphen		0.0010	B;.;.;.
Vest4		0.30
MutPred		0.57		Gain of disorder (P = 0.0684);Gain of disorder (P = 0.0684);Gain of disorder (P = 0.0684);Gain of disorder (P = 0.0684);
MVP		0.77
MPC		0.54
ClinPred		0.77	D
GERP RS		2.8
Varity_R		0.23
gMVP		0.69

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88717415;