rs1049254

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.521T>C(p.Val174Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,530,710 control chromosomes in the GnomAD database, including 302,624 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V174delinsAA) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.69 ( 36615 hom., cov: 34)

Exomes 𝑓: 0.62 ( 266009 hom. )

Consequence

CYBA
NM_000101.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -1.85

Publications

51 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=8.0484614E-7).

BP6

Variant 16-88643420-A-G is Benign according to our data. Variant chr16-88643420-A-G is described in ClinVar as Benign. ClinVar VariationId is 198042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 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.521T>C	p.Val174Ala	missense	Exon 6 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.521T>C	p.Val174Ala	missense	Exon 6 of 6	ENSP00000261623.3	P13498
CYBA	ENST00000967613.1		c.569T>C	p.Val190Ala	missense	Exon 7 of 7	ENSP00000637672.1
CYBA	ENST00000696160.1		c.548T>C	p.Val183Ala	missense	Exon 7 of 7	ENSP00000512450.1	A0A8Q3WL20

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104313

AN:

151816

Hom.:

36568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.831

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.606

Gnomad OTH

AF:

0.676

GnomAD2 exomes

AF:

0.648

AC:

81217

AN:

125396

AF XY:

0.650

show subpopulations

Gnomad AFR exome

AF:

0.820

Gnomad AMR exome

AF:

0.609

Gnomad ASJ exome

AF:

0.702

Gnomad EAS exome

AF:

0.741

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.600

Gnomad OTH exome

AF:

0.637

GnomAD4 exome

AF:

0.619

AC:

853140

AN:

1378782

Hom.:

266009

Cov.:

AF XY:

0.620

AC XY:

421618

AN XY:

680068

show subpopulations

African (AFR)

AF:

0.836

AC:

25128

AN:

30072

American (AMR)

AF:

0.618

AC:

21428

AN:

34662

Ashkenazi Jewish (ASJ)

AF:

0.699

AC:

17284

AN:

24718

East Asian (EAS)

AF:

0.796

AC:

27661

AN:

34770

South Asian (SAS)

AF:

0.696

AC:

54494

AN:

78244

European-Finnish (FIN)

AF:

0.645

AC:

26374

AN:

40882

Middle Eastern (MID)

AF:

0.690

AC:

3059

AN:

4432

European-Non Finnish (NFE)

AF:

0.597

AC:

641316

AN:

1073748

Other (OTH)

AF:

0.636

AC:

36396

AN:

57254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

17898

35797

53695

71594

89492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17932

35864

53796

71728

89660

<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:

0.687

AC:

104409

AN:

151928

Hom.:

36615

Cov.:

AF XY:

0.691

AC XY:

51337

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.831

AC:

34475

AN:

41468

American (AMR)

AF:

0.646

AC:

9880

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.692

AC:

2402

AN:

3472

East Asian (EAS)

AF:

0.759

AC:

3880

AN:

5110

South Asian (SAS)

AF:

0.708

AC:

3418

AN:

4826

European-Finnish (FIN)

AF:

0.668

AC:

7067

AN:

10576

Middle Eastern (MID)

AF:

0.741

AC:

215

AN:

290

European-Non Finnish (NFE)

AF:

0.606

AC:

41143

AN:

67876

Other (OTH)

AF:

0.675

AC:

1426

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1657

3313

4970

6626

8283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.642

Hom.:

6360

Bravo

AF:

0.691

TwinsUK

AF:

0.593

AC:

2197

ALSPAC

AF:

0.594

AC:

2288

ESP6500AA

AF:

0.821

AC:

1815

ESP6500EA

AF:

0.628

AC:

3364

ExAC

AF:

0.505

AC:

26874

Asia WGS

AF:

0.743

AC:

2576

AN:

3462

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (2)

not provided (3)

Chronic granulomatous disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.029

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.23

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.12

MetaRNN

Benign

8.0e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.4

PhyloP100

-1.9

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.22

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.025

MPC

0.20

ClinPred

0.0029

GERP RS

-7.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.017

gMVP

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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