rs4782308

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.203+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 1,580,492 control chromosomes in the GnomAD database, including 353,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31958 hom., cov: 33)

Exomes 𝑓: 0.67 ( 321214 hom. )

Consequence

CYBA
NM_000101.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00300

Publications

13 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: G2P, Labcorp Genetics (formerly Invitae)
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 (BayesDel_noAF=-0.82).

BP6

Variant 16-88647065-G-A is Benign according to our data. Variant chr16-88647065-G-A is described in ClinVar as Benign. ClinVar VariationId is 1172931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	NM_000101.4	MANE Select	c.203+36C>T		intron	N/A	NP_000092.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYBA	ENST00000261623.8	TSL:1 MANE Select	c.203+36C>T	intron	N/A	ENSP00000261623.3
CYBA	ENST00000569359.5	TSL:1	c.203+36C>T	intron	N/A	ENSP00000456079.1
CYBA	ENST00000562209.1	TSL:5	n.257C>T	non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.642

AC:

97613

AN:

151952

Hom.:

31936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.862

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.819

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.625

GnomAD2 exomes

AF:

0.680

AC:

152263

AN:

223910

AF XY:

0.672

show subpopulations

Gnomad AFR exome

AF:

0.523

Gnomad AMR exome

AF:

0.764

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.856

Gnomad FIN exome

AF:

0.812

Gnomad NFE exome

AF:

0.657

Gnomad OTH exome

AF:

0.648

GnomAD4 exome

AF:

0.668

AC:

953492

AN:

1428422

Hom.:

321214

Cov.:

AF XY:

0.666

AC XY:

473340

AN XY:

711196

show subpopulations

African (AFR)

AF:

0.520

AC:

17063

AN:

32830

American (AMR)

AF:

0.753

AC:

32353

AN:

42952

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

14730

AN:

25850

East Asian (EAS)

AF:

0.862

AC:

33537

AN:

38928

South Asian (SAS)

AF:

0.616

AC:

52192

AN:

84758

European-Finnish (FIN)

AF:

0.806

AC:

38239

AN:

47472

Middle Eastern (MID)

AF:

0.564

AC:

3225

AN:

5714

European-Non Finnish (NFE)

AF:

0.663

AC:

723194

AN:

1090618

Other (OTH)

AF:

0.657

AC:

38959

AN:

59300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

14935

29870

44805

59740

74675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18738

37476

56214

74952

93690

<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:

0.642

AC:

97674

AN:

152070

Hom.:

31958

Cov.:

AF XY:

0.651

AC XY:

48376

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.521

AC:

21617

AN:

41452

American (AMR)

AF:

0.717

AC:

10958

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.567

AC:

1966

AN:

3470

East Asian (EAS)

AF:

0.863

AC:

4448

AN:

5156

South Asian (SAS)

AF:

0.621

AC:

2994

AN:

4824

European-Finnish (FIN)

AF:

0.819

AC:

8691

AN:

10608

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.660

AC:

44890

AN:

67966

Other (OTH)

AF:

0.626

AC:

1322

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1728

3455

5183

6910

8638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.633

Hom.:

5525

Bravo

AF:

0.632

Asia WGS

AF:

0.713

AC:

2480

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 86. Only high quality variants are reported.

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.2

(source)

DANN

Benign

0.84

PhyloP100

-0.0030

PromoterAI

0.018

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over