rs4595265

Variant names:

• chrX-37783152-G-T
• rs4595265
• NM_000397.4:c.142-338G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000397.4(CYBB):​c.142-338G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 111,257 control chromosomes in the GnomAD database, including 639 homozygotes. There are 3,881 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (639 hom., 3881 hem., cov: 23)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0980
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-37783152-G-T is Benign according to our data. Variant chrX-37783152-G-T is described in ClinVar as Benign. ClinVar VariationId is 1234945.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBB	NM_000397.4	c.142-338G>T		intron_variant	Intron 2 of 12	ENST00000378588.5	NP_000388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBB	ENST00000378588.5	c.142-338G>T		intron_variant	Intron 2 of 12	1	NM_000397.4	ENSP00000367851.4
ENSG00000250349	ENST00000465127.1	c.171+357152G>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 13155 AN: 111205 Hom.: 639 Cov.: 23

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0556

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.118 AC: 13156 AN: 111257 Hom.: 639 Cov.: 23 AF XY: 0.116 AC XY: 3881 AN XY: 33483

African (AFR) AF: 0.0391 AC: 1203 AN: 30736

American (AMR) AF: 0.152 AC: 1592 AN: 10454

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 449 AN: 2646

East Asian (EAS) AF: 0.0693 AC: 245 AN: 3534

South Asian (SAS) AF: 0.0888 AC: 240 AN: 2702

European-Finnish (FIN) AF: 0.130 AC: 751 AN: 5789

Middle Eastern (MID) AF: 0.0566 AC: 12 AN: 212

European-Non Finnish (NFE) AF: 0.159 AC: 8423 AN: 52988

Other (OTH) AF: 0.113 AC: 170 AN: 1511

Alfa AF: 0.140 Hom.: 1491

Bravo AF: 0.118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		0.098
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: rs4595265; hg19: chrX-37642405;