rs4673

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000101.4(CYBA):c.214T>C(p.Tyr72His) variant causes a missense change. The variant allele was found at a frequency of 0.672 in 1,612,206 control chromosomes in the GnomAD database, including 367,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32939 hom., cov: 32)

Exomes 𝑓: 0.67 ( 334674 hom. )

Consequence

CYBA
NM_000101.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:13O:1

Conservation

PhyloP100: 4.22

Publications

403 publications found

Variant links:

Genes affected

CYBA (HGNC:2577): (cytochrome b-245 alpha chain) Cytochrome b is comprised of a light chain (alpha) and a heavy chain (beta). This gene encodes the light, alpha subunit which has been proposed as a primary component of the microbicidal oxidase system of phagocytes. Mutations in this gene are associated with autosomal recessive chronic granulomatous disease (CGD), that is characterized by the failure of activated phagocytes to generate superoxide, which is important for the microbicidal activity of these cells. [provided by RefSeq, Jul 2008]

CYBA Gene-Disease associations (from GenCC):

granulomatous disease, chronic, autosomal recessive, cytochrome b-negative
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
chronic granulomatous disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CYBA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2247359E-6).

BP6

Variant 16-88646828-A-G is Benign according to our data. Variant chr16-88646828-A-G is described in ClinVar as Benign. ClinVar VariationId is 2263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000101.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	NM_000101.4	MANE Select	c.214T>C	p.Tyr72His	missense	Exon 4 of 6	NP_000092.2	P13498

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYBA	ENST00000261623.8	TSL:1 MANE Select	c.214T>C	p.Tyr72His	missense	Exon 4 of 6	ENSP00000261623.3	P13498
CYBA	ENST00000569359.5	TSL:1	c.214T>C	p.Tyr72His	missense	Exon 4 of 5	ENSP00000456079.1	H3BR52
CYBA	ENST00000696161.1		c.344T>C	p.Val115Ala	missense	Exon 4 of 6	ENSP00000512451.1	A0A8Q3WL26

Frequencies

GnomAD3 genomes

AF:

0.653

AC:

99158

AN:

151878

Hom.:

32915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.544

Gnomad AMI

AF:

0.690

Gnomad AMR

AF:

0.722

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.643

Gnomad FIN

AF:

0.824

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.636

GnomAD2 exomes

AF:

0.698

AC:

174863

AN:

250626

AF XY:

0.690

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.771

Gnomad ASJ exome

AF:

0.568

Gnomad EAS exome

AF:

0.914

Gnomad FIN exome

AF:

0.822

Gnomad NFE exome

AF:

0.668

Gnomad OTH exome

AF:

0.666

GnomAD4 exome

AF:

0.674

AC:

983701

AN:

1460210

Hom.:

334674

Cov.:

AF XY:

0.672

AC XY:

488360

AN XY:

726538

show subpopulations

African (AFR)

AF:

0.541

AC:

18100

AN:

33440

American (AMR)

AF:

0.760

AC:

33973

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

15147

AN:

26122

East Asian (EAS)

AF:

0.906

AC:

35974

AN:

39686

South Asian (SAS)

AF:

0.634

AC:

54683

AN:

86226

European-Finnish (FIN)

AF:

0.813

AC:

43211

AN:

53176

Middle Eastern (MID)

AF:

0.570

AC:

3288

AN:

5766

European-Non Finnish (NFE)

AF:

0.665

AC:

739154

AN:

1110744

Other (OTH)

AF:

0.666

AC:

40171

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

17882

35763

53645

71526

89408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19204

38408

57612

76816

96020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.653

AC:

99225

AN:

151996

Hom.:

32939

Cov.:

AF XY:

0.661

AC XY:

49133

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.543

AC:

22498

AN:

41424

American (AMR)

AF:

0.723

AC:

11043

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

2007

AN:

3468

East Asian (EAS)

AF:

0.910

AC:

4702

AN:

5166

South Asian (SAS)

AF:

0.643

AC:

3100

AN:

4822

European-Finnish (FIN)

AF:

0.824

AC:

8724

AN:

10592

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.663

AC:

45011

AN:

67926

Other (OTH)

AF:

0.639

AC:

1350

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1769

3537

5306

7074

8843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.657

Hom.:

159400

Bravo

AF:

0.643

TwinsUK

AF:

0.645

AC:

2393

ALSPAC

AF:

0.668

AC:

2573

ESP6500AA

AF:

0.553

AC:

2432

ESP6500EA

AF:

0.657

AC:

5646

ExAC

AF:

0.690

AC:

83753

Asia WGS

AF:

0.764

AC:

2654

AN:

3478

EpiCase

AF:

0.639

EpiControl

AF:

0.643

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (4)

not provided (3)

Chronic granulomatous disease (1)

CYBA POLYMORPHISM (1)

Very early onset inflammatory bowel disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.0000012

PhyloP100

4.2

PROVEAN

Uncertain

-4.0

ClinPred

0.063

GERP RS

3.5

PromoterAI

0.27

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.19

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over