rs5917471

chrX-37793265-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.338-400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 107,862 control chromosomes in the GnomAD database, including 13,763 homozygotes. There are 15,984 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 0.54 (13763 hom., 15984 hem., cov: 20)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBB	NM_000397.4	c.338-400C>T		intron_variant		ENST00000378588.5
CYBB	XM_047441855.1	c.32-400C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBB	ENST00000378588.5	c.338-400C>T		intron_variant		1	NM_000397.4	P1
CYBB	ENST00000696171.1	c.242-400C>T		intron_variant
CYBB	ENST00000696170.1	c.337+1206C>T		intron_variant, NMD_transcript_variant
CYBB	ENST00000696172.1	c.337+1206C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.542 AC: 58426 AN: 107807 Hom.: 13759 Cov.: 20 AF XY: 0.525 AC XY: 15925 AN XY: 30305

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.542 AC: 58486 AN: 107862 Hom.: 13763 Cov.: 20 AF XY: 0.526 AC XY: 15984 AN XY: 30370

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.0956

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.512

Alfa AF: 0.449 Hom.: 24711

Bravo AF: 0.555

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.16
Dann	Benign	0.46

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: rs5917471; hg19: chrX-37652518;