rs5964125

chrX-37799202-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000397.4(CYBB):c.804+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 698,190 control chromosomes in the GnomAD database, including 7,066 homozygotes. There are 35,503 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (1072 hom., 5460 hem., cov: 23)
  • Exomes 𝑓: 0.17 (5994 hom. 30043 hem.)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.38

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-37799202-A-G is Benign according to our data. Variant chrX-37799202-A-G is described in ClinVar as [Benign]. Clinvar id is 1185172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-37799202-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBB	NM_000397.4	c.804+118A>G		intron_variant		ENST00000378588.5
CYBB	XM_047441855.1	c.498+118A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBB	ENST00000378588.5	c.804+118A>G		intron_variant		1	NM_000397.4	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 18431 AN: 111711 Hom.: 1069 Cov.: 23 AF XY: 0.160 AC XY: 5448 AN XY: 33971

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0928

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.170 AC: 99980 AN: 586426 Hom.: 5994 AF XY: 0.185 AC XY: 30043 AN XY: 162768

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.0486

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.165 AC: 18443 AN: 111764 Hom.: 1072 Cov.: 23 AF XY: 0.160 AC XY: 5460 AN XY: 34034

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.0667

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.148

Alfa AF: 0.171 Hom.: 1002

Bravo AF: 0.169

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Granulomatous disease, chronic, X-linked Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	9.0
Dann	Benign	0.85

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: rs5964125; hg19: chrX-37658455;