X-37780111-A-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_000397.4(CYBB):c.34A>C(p.Ile12Leu) variant causes a missense change. 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: CYBB NM_000397.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.44

Genes affected

CYBB (HGNC:2578): (cytochrome b-245 beta chain) Cytochrome b (-245) is composed of cytochrome b alpha (CYBA) and beta (CYBB) chain. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes. CYBB deficiency is one of five described biochemical defects associated with chronic granulomatous disease (CGD). In this disorder, there is decreased activity of phagocyte NADPH oxidase; neutrophils are able to phagocytize bacteria but cannot kill them in the phagocytic vacuoles. The cause of the killing defect is an inability to increase the cell's respiration and consequent failure to deliver activated oxygen into the phagocytic vacuole. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3316649).
• BP6: Variant X-37780111-A-C is Benign according to our data. Variant chrX-37780111-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 191245.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-37780111-A-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBB	NM_000397.4	c.34A>C	p.Ile12Leu	missense_variant	1/13	ENST00000378588.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBB	ENST00000378588.5	c.34A>C	p.Ile12Leu	missense_variant	1/13	1	NM_000397.4	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

research

Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre

Sep 28, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Benign	21
Dann	Benign	0.94
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.15	D
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.96	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.28
Sift	Benign	0.55	T
Sift4G	Benign	0.63	T
Polyphen		0.21	B
Vest4		0.34
MutPred		0.35		Gain of glycosylation at S11 (P = 0.2255);
MVP		0.91
MPC		0.61
ClinPred		0.48	T
GERP RS		5.4
Varity_R		0.30
gMVP		0.80

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

LitVar

Other links and lift over

dbSNP: rs797044560; hg19: chrX-37639364;