Variant rs7059081 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000397.4(CYBB):c.141+48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 842,855 control chromosomes in the GnomAD database, including 1,519 homozygotes. There are 15,643 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 163 hom., 1612 hem., cov: 22)

Exomes 𝑓: 0.069 ( 1356 hom. 14031 hem. )

Consequence

CYBB
NM_000397.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0380

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-37782231-C-G is Benign according to our data. Variant chrX-37782231-C-G is described in ClinVar as [Benign]. Clinvar id is 1246166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-37782231-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBB	NM_000397.4 linkuse as main transcript	c.141+48C>G		intron_variant		ENST00000378588.5	NP_000388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBB	ENST00000378588.5 linkuse as main transcript	c.141+48C>G		intron_variant		1	NM_000397.4	ENSP00000367851	P1

Frequencies

GnomAD3 genomes

AF:

0.0517

AC:

5785

AN:

111970

Hom.:

163

Cov.:

AF XY:

0.0472

AC XY:

1612

AN XY:

34148

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0675

Gnomad AMR

AF:

0.0529

Gnomad ASJ

AF:

0.0740

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0125

Gnomad FIN

AF:

0.0699

Gnomad MID

AF:

0.0464

Gnomad NFE

AF:

0.0775

Gnomad OTH

AF:

0.0554

GnomAD3 exomes

AF:

0.0508

AC:

8848

AN:

174201

Hom.:

199

AF XY:

0.0494

AC XY:

2965

AN XY:

60049

show subpopulations

Gnomad AFR exome

AF:

0.00942

Gnomad AMR exome

AF:

0.0322

Gnomad ASJ exome

AF:

0.0724

Gnomad EAS exome

AF:

0.000898

Gnomad SAS exome

AF:

0.0133

Gnomad FIN exome

AF:

0.0727

Gnomad NFE exome

AF:

0.0750

Gnomad OTH exome

AF:

0.0633

GnomAD4 exome

AF:

0.0687

AC:

50214

AN:

730831

Hom.:

1356

Cov.:

AF XY:

0.0694

AC XY:

14031

AN XY:

202299

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.0345

Gnomad4 ASJ exome

AF:

0.0704

Gnomad4 EAS exome

AF:

0.000281

Gnomad4 SAS exome

AF:

0.0142

Gnomad4 FIN exome

AF:

0.0751

Gnomad4 NFE exome

AF:

0.0818

Gnomad4 OTH exome

AF:

0.0665

GnomAD4 genome

AF:

0.0516

AC:

5782

AN:

112024

Hom.:

163

Cov.:

AF XY:

0.0471

AC XY:

1612

AN XY:

34212

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0527

Gnomad4 ASJ

AF:

0.0740

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0125

Gnomad4 FIN

AF:

0.0699

Gnomad4 NFE

AF:

0.0775

Gnomad4 OTH

AF:

0.0548

Alfa

AF:

0.0612

Hom.:

523

Bravo

AF:

0.0500

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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