rs5917471

Variant names:

• chrX-37793265-C-T
• rs5917471
• NM_000397.4:c.338-400C>T

Variant summary

Our verdict is Benign. The variant received -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. 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
• Publications: 10 publications found

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]

CYBB Gene-Disease associations (from GenCC):

• granulomatous disease, chronic, X-linked

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• chronic granulomatous disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency

  Inheritance: Unknown, XL Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000397.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBB	NM_000397.4	MANE Select	c.338-400C>T		intron	N/A	NP_000388.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBB	ENST00000378588.5	TSL:1 MANE Select	c.338-400C>T		intron	N/A	ENSP00000367851.4	P04839
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+367265C>T		intron	N/A	ENSP00000417050.1	B4E171
	CYBB	ENST00000968558.1		c.338-400C>T		intron	N/A	ENSP00000638617.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 58426 AN: 107807 Hom.: 13759 Cov.: 20

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

African (AFR) AF: 0.903 AC: 26691 AN: 29567

American (AMR) AF: 0.384 AC: 3807 AN: 9916

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1210 AN: 2602

East Asian (EAS) AF: 0.0956 AC: 331 AN: 3461

South Asian (SAS) AF: 0.479 AC: 1188 AN: 2479

European-Finnish (FIN) AF: 0.396 AC: 2171 AN: 5477

Middle Eastern (MID) AF: 0.589 AC: 126 AN: 214

European-Non Finnish (NFE) AF: 0.420 AC: 21845 AN: 51995

Other (OTH) AF: 0.512 AC: 756 AN: 1477

Alfa AF: 0.458 Hom.: 38627

Bravo AF: 0.555

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.46
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5917471;

hg19: chrX-37652518;