Variant rs34834015 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000397.4(CYBB):c.1314+19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,203,177 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 6 hem. )

Consequence

CYBB
NM_000397.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.678

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-37805187-C-G is Benign according to our data. Variant chrX-37805187-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1593327.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBB	NM_000397.4 linkuse as main transcript	c.1314+19C>G		intron_variant		ENST00000378588.5
CYBB	XM_047441855.1 linkuse as main transcript	c.1008+19C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
CYBB	ENST00000378588.5 linkuse as main transcript	c.1314+19C>G	intron_variant	1	NM_000397.4	P1
CYBB	ENST00000696171.1 linkuse as main transcript	c.1218+19C>G	intron_variant
CYBB	ENST00000696170.1 linkuse as main transcript	c.*823+19C>G	intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112020

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34230

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000167

AC:

AN:

179935

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

65093

show subpopulations

Gnomad AFR exome

AF:

0.000230

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000156

AC:

AN:

1091103

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

357129

show subpopulations

Gnomad4 AFR exome

AF:

0.000343

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000120

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.0000446

AC:

AN:

112074

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34294

show subpopulations

Gnomad4 AFR

AF:

0.000163

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Granulomatous disease, chronic, X-linked

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 05, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

0.20

Dann

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over