16-88650978-T-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.36A>G(p.Glu12Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,596,232 control chromosomes in the GnomAD database, including 797,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75697 hom., cov: 34)

Exomes 𝑓: 1.0 ( 721466 hom. )

Consequence

CYBA
NM_000101.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.114

Publications

17 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 16-88650978-T-C is Benign according to our data. Variant chr16-88650978-T-C is described in ClinVar as Benign. ClinVar VariationId is 1168658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.114 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4 link	c.36A>G	p.Glu12Glu	synonymous_variant	Exon 1 of 6	ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4 link	c.36A>G	p.Glu12Glu	synonymous_variant	Exon 1 of 6		XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8 link	c.36A>G	p.Glu12Glu	synonymous_variant	Exon 1 of 6	1	NM_000101.4	ENSP00000261623.3

Frequencies

GnomAD3 genomes

AF:

0.997

AC:

151738

AN:

152204

Hom.:

75640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.990

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.999

GnomAD2 exomes

AF:

0.999

AC:

215897

AN:

216058

AF XY:

1.00

show subpopulations

Gnomad AFR exome

AF:

0.989

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1443413

AN:

1443910

Hom.:

721466

Cov.:

AF XY:

1.00

AC XY:

716748

AN XY:

716940

show subpopulations

African (AFR)

AF:

0.988

AC:

32575

AN:

32980

American (AMR)

AF:

0.999

AC:

42958

AN:

42984

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

25736

AN:

25736

East Asian (EAS)

AF:

1.00

AC:

38538

AN:

38538

South Asian (SAS)

AF:

1.00

AC:

83791

AN:

83794

European-Finnish (FIN)

AF:

1.00

AC:

49801

AN:

49802

Middle Eastern (MID)

AF:

1.00

AC:

5695

AN:

5696

European-Non Finnish (NFE)

AF:

1.00

AC:

1104770

AN:

1104778

Other (OTH)

AF:

0.999

AC:

59549

AN:

59602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21560

43120

64680

86240

107800

<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:

0.997

AC:

151854

AN:

152322

Hom.:

75697

Cov.:

AF XY:

0.997

AC XY:

74258

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.990

AC:

41146

AN:

41580

American (AMR)

AF:

0.998

AC:

15279

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5174

AN:

5174

South Asian (SAS)

AF:

1.00

AC:

4834

AN:

4834

European-Finnish (FIN)

AF:

1.00

AC:

10628

AN:

10628

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68006

AN:

68008

Other (OTH)

AF:

0.999

AC:

2109

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.999

Hom.:

26392

Bravo

AF:

0.996

Asia WGS

AF:

0.999

AC:

3472

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

- -

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

Benign:2

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Chronic granulomatous disease

Benign:1

Jan 11, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.11

PromoterAI

0.087

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over