NM_000101.4:c.237G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000101.4(CYBA):c.237G>C(p.Leu79Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 1,613,928 control chromosomes in the GnomAD database, including 795 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. L79L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.041 ( 409 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 386 hom. )

Consequence

CYBA
NM_000101.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.00300

Publications

3 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=0.0016738176).

BP6

Variant 16-88646805-C-G is Benign according to our data. Variant chr16-88646805-C-G is described in ClinVar as Benign. ClinVar VariationId is 255126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.003 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 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.237G>C	p.Leu79Leu	synonymous	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.237G>C	p.Leu79Leu	synonymous	Exon 4 of 6	ENSP00000261623.3	P13498
CYBA	ENST00000569359.5	TSL:1	c.237G>C	p.Leu79Leu	synonymous	Exon 4 of 5	ENSP00000456079.1	H3BR52
CYBA	ENST00000696161.1		c.367G>C	p.Val123Leu	missense	Exon 4 of 6	ENSP00000512451.1	A0A8Q3WL26

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6174

AN:

152078

Hom.:

407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0268

GnomAD2 exomes

AF:

0.0102

AC:

2562

AN:

251036

AF XY:

0.00763

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.00654

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00402

AC:

5874

AN:

1461732

Hom.:

386

Cov.:

AF XY:

0.00339

AC XY:

2463

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.146

AC:

4890

AN:

33472

American (AMR)

AF:

0.00693

AC:

310

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000336

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53310

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000710

AC:

AN:

1111974

Other (OTH)

AF:

0.00911

AC:

550

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

299

599

898

1198

1497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

296

444

592

740

<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:

0.0406

AC:

6182

AN:

152196

Hom.:

409

Cov.:

AF XY:

0.0392

AC XY:

2915

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.142

AC:

5876

AN:

41490

American (AMR)

AF:

0.0144

AC:

220

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68012

Other (OTH)

AF:

0.0265

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

270

540

809

1079

1349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.00444

Hom.:

Bravo

AF:

0.0460

ESP6500AA

AF:

0.143

AC:

627

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.0126

AC:

1536

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Chronic granulomatous disease (1)

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

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.8

(source)

DANN

Benign

0.87

FATHMM_MKL

Benign

0.54

MetaRNN

Benign

0.0017

PhyloP100

0.0030

PROVEAN

Benign

-1.7

GERP RS

0.68

PromoterAI

-0.038

Neutral

(source)

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)

0.0

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