rs4595265

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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 AF XY: 0.116 AC XY: 3874 AN XY: 33421

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

Gnomad4 AFR AF: 0.0391

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0693

Gnomad4 SAS AF: 0.0888

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.113

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

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: rs4595265; hg19: chrX-37642405;