Variant rs2228117 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000397.4(CYBB):c.1002G>A(p.Lys334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00969 in 1,209,331 control chromosomes in the GnomAD database, including 698 homozygotes. There are 3,144 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 ( 374 hom., 1570 hem., cov: 22)

Exomes 𝑓: 0.0054 ( 324 hom. 1574 hem. )

Consequence

CYBB
NM_000397.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.153

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-37803981-G-A is Benign according to our data. Variant chrX-37803981-G-A is described in ClinVar as [Benign]. Clinvar id is 464971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-37803981-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.153 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBB	NM_000397.4 linkuse as main transcript	c.1002G>A	p.Lys334=	synonymous_variant	9/13	ENST00000378588.5
CYBB	XM_047441855.1 linkuse as main transcript	c.696G>A	p.Lys232=	synonymous_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CYBB	ENST00000378588.5 linkuse as main transcript	c.1002G>A	p.Lys334=	synonymous_variant	9/13	1	NM_000397.4	P1
CYBB	ENST00000696171.1 linkuse as main transcript	c.906G>A	p.Lys302=	synonymous_variant	8/12
CYBB	ENST00000492288.1 linkuse as main transcript	n.427G>A		non_coding_transcript_exon_variant	4/4	3
CYBB	ENST00000696170.1 linkuse as main transcript	c.*511G>A		3_prime_UTR_variant, NMD_transcript_variant	8/12

Frequencies

GnomAD3 genomes

AF:

0.0518

AC:

5771

AN:

111434

Hom.:

373

Cov.:

AF XY:

0.0465

AC XY:

1564

AN XY:

33668

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0296

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00113

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000546

Gnomad OTH

AF:

0.0347

GnomAD3 exomes

AF:

0.0153

AC:

2795

AN:

183062

Hom.:

174

AF XY:

0.0102

AC XY:

691

AN XY:

67652

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000367

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000429

Gnomad OTH exome

AF:

0.00797

GnomAD4 exome

AF:

0.00542

AC:

5945

AN:

1097846

Hom.:

324

Cov.:

AF XY:

0.00433

AC XY:

1574

AN XY:

363404

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000425

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000244

Gnomad4 OTH exome

AF:

0.0137

GnomAD4 genome

AF:

0.0518

AC:

5779

AN:

111485

Hom.:

374

Cov.:

AF XY:

0.0465

AC XY:

1570

AN XY:

33729

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.0296

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00113

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000546

Gnomad4 OTH

AF:

0.0343

Alfa

AF:

0.0224

Hom.:

221

Bravo

AF:

0.0601

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	-	- -

Granulomatous disease, chronic, X-linked

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Chronic granulomatous disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

DANN

Benign

0.73

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