NM_000101.4:c.381T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000101.4(CYBA):c.381T>C(p.Arg127Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 1,532,918 control chromosomes in the GnomAD database, including 1,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R127R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.025 ( 74 hom., cov: 33)

Exomes 𝑓: 0.033 ( 955 hom. )

Consequence

CYBA
NM_000101.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.72

Publications

9 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066922307).

BP6

Variant 16-88643560-A-G is Benign according to our data. Variant chr16-88643560-A-G is described in ClinVar as Benign. ClinVar VariationId is 255127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.72 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0248 (3771/151950) while in subpopulation NFE AF = 0.0385 (2618/67916). AF 95% confidence interval is 0.0373. There are 74 homozygotes in GnomAd4. There are 1810 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 74 AR gene

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.381T>C	p.Arg127Arg	synonymous	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.381T>C	p.Arg127Arg	synonymous	Exon 6 of 6	ENSP00000261623.3	P13498
CYBA	ENST00000696161.1		c.511T>C	p.Trp171Arg	missense	Exon 6 of 6	ENSP00000512451.1	A0A8Q3WL26
CYBA	ENST00000565588.6	TSL:2	c.391T>C	p.Trp131Arg	missense	Exon 6 of 6	ENSP00000455537.2	H3BPZ7

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3771

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00593

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0415

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0209

AC:

2715

AN:

130142

AF XY:

0.0197

show subpopulations

Gnomad AFR exome

AF:

0.00422

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0416

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0223

GnomAD4 exome

AF:

0.0333

AC:

46053

AN:

1380968

Hom.:

955

Cov.:

AF XY:

0.0321

AC XY:

21906

AN XY:

681722

show subpopulations

African (AFR)

AF:

0.00527

AC:

166

AN:

31496

American (AMR)

AF:

0.0149

AC:

530

AN:

35644

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

297

AN:

25076

East Asian (EAS)

AF:

0.0000840

AC:

AN:

35710

South Asian (SAS)

AF:

0.00143

AC:

113

AN:

79136

European-Finnish (FIN)

AF:

0.0415

AC:

1430

AN:

34488

Middle Eastern (MID)

AF:

0.00222

AC:

AN:

4060

European-Non Finnish (NFE)

AF:

0.0390

AC:

42051

AN:

1077746

Other (OTH)

AF:

0.0252

AC:

1454

AN:

57612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2322

4645

6967

9290

11612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1560

3120

4680

6240

7800

<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:

0.0248

AC:

3771

AN:

151950

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1810

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.00594

AC:

246

AN:

41422

American (AMR)

AF:

0.0243

AC:

371

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00311

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0415

AC:

439

AN:

10590

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0385

AC:

2618

AN:

67916

Other (OTH)

AF:

0.0152

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

181

362

542

723

904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0200

Hom.:

Bravo

AF:

0.0217

TwinsUK

AF:

0.0299

AC:

111

ALSPAC

AF:

0.0371

AC:

143

ESP6500AA

AF:

0.00281

AC:

ESP6500EA

AF:

0.0240

AC:

147

ExAC

AF:

0.00744

AC:

542

Asia WGS

AF:

0.00145

AC:

AN:

3462

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Chronic granulomatous disease (1)

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.069

(source)

DANN

Benign

0.57

FATHMM_MKL

Benign

0.010

MetaRNN

Benign

0.0067

PhyloP100

-4.7

PROVEAN

Pathogenic

-7.0

GERP RS

-8.4

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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