Variant rs5964125 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.804+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 698,190 control chromosomes in the GnomAD database, including 7,066 homozygotes. There are 35,503 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 1072 hom., 5460 hem., cov: 23)

Exomes 𝑓: 0.17 ( 5994 hom. 30043 hem. )

Consequence

CYBB
NM_000397.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.38

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:

ENSG00000250349 (HGNC:):

ENSG00000250349 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=-0.8).

BP6

Variant X-37799202-A-G is Benign according to our data. Variant chrX-37799202-A-G is described in ClinVar as [Benign]. Clinvar id is 1185172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-37799202-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 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.804+118A>G		intron_variant		ENST00000378588.5	NP_000388.2	P04839A0A0S2Z3S6
CYBB	XM_047441855.1 linkuse as main transcript	c.498+118A>G		intron_variant			XP_047297811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBB	ENST00000378588.5 linkuse as main transcript	c.804+118A>G		intron_variant		1	NM_000397.4	ENSP00000367851.4		P04839
ENSG00000250349	ENST00000465127.1 linkuse as main transcript	c.171+373202A>G		intron_variant		5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

18431

AN:

111711

Hom.:

1069

Cov.:

AF XY:

0.160

AC XY:

5448

AN XY:

33971

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.0674

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.0928

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.145

GnomAD4 exome

AF:

0.170

AC:

99980

AN:

586426

Hom.:

5994

AF XY:

0.185

AC XY:

30043

AN XY:

162768

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.0486

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.173

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.165

AC:

18443

AN:

111764

Hom.:

1072

Cov.:

AF XY:

0.160

AC XY:

5460

AN XY:

34034

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.0667

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.171

Hom.:

1002

Bravo

AF:

0.169

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Granulomatous disease, chronic, X-linked

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.0

DANN

Benign

0.85

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

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