rs6520785

Variant names:

• chrX-37785172-C-G
• rs6520785
• NM_000397.4:c.252+1572C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-37785172-C-G
• chrX-37785172-C-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.252+1572C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 111,416 control chromosomes in the GnomAD database, including 6,221 homozygotes. There are 10,206 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 0.32 (6221 hom., 10206 hem., cov: 23)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 1 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: XL, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.693 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.252+1572C>G		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.252+1572C>G		intron	N/A	ENSP00000367851.4	P04839
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+359172C>G		intron	N/A	ENSP00000417050.1	B4E171
	CYBB	ENST00000968558.1		c.252+1572C>G		intron	N/A	ENSP00000638617.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 35083 AN: 111366 Hom.: 6214 Cov.: 23

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.0933

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.315 AC: 35143 AN: 111416 Hom.: 6221 Cov.: 23 AF XY: 0.303 AC XY: 10206 AN XY: 33686

African (AFR) AF: 0.701 AC: 21409 AN: 30550

American (AMR) AF: 0.241 AC: 2535 AN: 10526

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 534 AN: 2637

East Asian (EAS) AF: 0.0689 AC: 245 AN: 3555

South Asian (SAS) AF: 0.198 AC: 539 AN: 2721

European-Finnish (FIN) AF: 0.132 AC: 794 AN: 6003

Middle Eastern (MID) AF: 0.125 AC: 27 AN: 216

European-Non Finnish (NFE) AF: 0.162 AC: 8596 AN: 53006

Other (OTH) AF: 0.263 AC: 401 AN: 1527

Alfa AF: 0.243 Hom.: 1572

Bravo AF: 0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.28
PhyloP100		-0.39
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

Other links and lift over

dbSNP: rs6520785; hg19: chrX-37644425;