rs5964151

chrX-37811476-T-G

Variant summary

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

The NM_000397.4(CYBB):c.*559T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 119,218 control chromosomes in the GnomAD database, including 2,188 homozygotes. There are 6,999 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 0.21 (2098 hom., 6680 hem., cov: 22)
  • Exomes 𝑓: 0.16 (90 hom. 319 hem.)
• Consequence: CYBB NM_000397.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -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 = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBB	NM_000397.4	c.*559T>G		3_prime_UTR_variant	13/13	ENST00000378588.5
CYBB	XM_047441855.1	c.*559T>G		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBB	ENST00000378588.5	c.*559T>G		3_prime_UTR_variant	13/13	1	NM_000397.4	P1
CYBB	ENST00000696170.1	c.*1781T>G		3_prime_UTR_variant, NMD_transcript_variant	12/12

Frequencies

GnomAD3 genomes AF: 0.212 AC: 23526 AN: 110912 Hom.: 2098 Cov.: 22 AF XY: 0.201 AC XY: 6657 AN XY: 33164

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0979

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.157 AC: 1298 AN: 8256 Hom.: 90 Cov.: 0 AF XY: 0.182 AC XY: 319 AN XY: 1748

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.0826

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.212 AC: 23547 AN: 110962 Hom.: 2098 Cov.: 22 AF XY: 0.201 AC XY: 6680 AN XY: 33224

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.0656

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.189

Alfa AF: 0.177 Hom.: 8943

Bravo AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.075
Dann	Benign	0.77

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: rs5964151; hg19: chrX-37670729;