rs12848910

Positions:

• chrX-37806992-A-G

Variant summary

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

The NM_000397.4(CYBB):​c.1461+459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 110,697 control chromosomes in the GnomAD database, including 202 homozygotes. There are 1,893 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 0.059 (202 hom., 1893 hem., cov: 22)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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]

ENSG00000250349 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBB	NM_000397.4	c.1461+459A>G		intron_variant		ENST00000378588.5	NP_000388.2
CYBB	XM_047441855.1	c.1155+459A>G		intron_variant			XP_047297811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBB	ENST00000378588.5	c.1461+459A>G		intron_variant		1	NM_000397.4	ENSP00000367851.4
ENSG00000250349	ENST00000465127.1	c.171+380992A>G		intron_variant		5		ENSP00000417050.1
CYBB	ENST00000696171.1	c.1365+459A>G		intron_variant				ENSP00000512462.1
CYBB	ENST00000696170.1	n.*970+459A>G		intron_variant				ENSP00000512461.1

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 6538 AN: 110650 Hom.: 203 Cov.: 22 AF XY: 0.0576 AC XY: 1893 AN XY: 32888

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0460

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0590 AC: 6534 AN: 110697 Hom.: 202 Cov.: 22 AF XY: 0.0575 AC XY: 1893 AN XY: 32945

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0982

Gnomad4 NFE AF: 0.0911

Gnomad4 OTH AF: 0.0525

Alfa AF: 0.0841 Hom.: 2086

Bravo AF: 0.0523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.78

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: rs12848910; hg19: chrX-37666245;