rs797044560

Variant names:

• chrX-37780111-A-C
• rs797044560
• NM_000397.4:c.34A>C

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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]

CYBB Gene-Disease associations (from GenCC):

• granulomatous disease, chronic, X-linked

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• chronic granulomatous disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency

  Inheritance: XL, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3316649).
• 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 VariationId is 191245.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBB	NM_000397.4	c.34A>C	p.Ile12Leu	missense_variant	Exon 1 of 13	ENST00000378588.5	NP_000388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBB	ENST00000378588.5	c.34A>C	p.Ile12Leu	missense_variant	Exon 1 of 13	1	NM_000397.4	ENSP00000367851.4
ENSG00000250349	ENST00000465127.1	c.171+354111A>C		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 28, 2016

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

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
PhyloP100		4.4
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
PromoterAI		0.0022	Neutral
Varity_R		0.30
gMVP		0.80
Mutation Taster		=285/15	polymorphism

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

Other links and lift over

dbSNP: rs797044560; hg19: chrX-37639364;