rs4827298

chrX-37792410-T-C

Variant summary

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

The NM_000397.4(CYBB):c.337+351T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 109,873 control chromosomes in the GnomAD database, including 10,079 homozygotes. There are 12,869 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 0.42 (10079 hom., 12869 hem., cov: 22)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBB	NM_000397.4	c.337+351T>C		intron_variant		ENST00000378588.5
CYBB	XM_047441855.1	c.31+351T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBB	ENST00000378588.5	c.337+351T>C		intron_variant		1	NM_000397.4	P1
CYBB	ENST00000696171.1	c.241+351T>C		intron_variant
CYBB	ENST00000696170.1	c.337+351T>C		intron_variant, NMD_transcript_variant
CYBB	ENST00000696172.1	c.337+351T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.418 AC: 45885 AN: 109834 Hom.: 10070 Cov.: 22 AF XY: 0.398 AC XY: 12822 AN XY: 32246

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.418 AC: 45943 AN: 109873 Hom.: 10079 Cov.: 22 AF XY: 0.398 AC XY: 12869 AN XY: 32295

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0681

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.369

Alfa AF: 0.330 Hom.: 3545

Bravo AF: 0.443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.31

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: rs4827298; hg19: chrX-37651663;