rs6520785

chrX-37785172-C-GchrX-37785172-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000397.4(CYBB):c.252+1572C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 111,416 control chromosomes in the GnomAD database, including 6,221 homozygotes. There are 10,206 hemizygotes in GnomAD. 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: 𝑓 0.32 (6221 hom., 10206 hem., cov: 23)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBB	NM_000397.4	c.252+1572C>G		intron_variant		ENST00000378588.5
CYBB	XM_047441855.1	c.-179+1572C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBB	ENST00000378588.5	c.252+1572C>G		intron_variant		1	NM_000397.4	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 35083 AN: 111366 Hom.: 6214 Cov.: 23 AF XY: 0.302 AC XY: 10155 AN XY: 33626

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.0933

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.315 AC: 35143 AN: 111416 Hom.: 6221 Cov.: 23 AF XY: 0.303 AC XY: 10206 AN XY: 33686

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.0689

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.263

Alfa AF: 0.243 Hom.: 1572

Bravo AF: 0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.24
Dann	Benign	0.28

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: rs6520785; hg19: chrX-37644425;