dbSNP rs3794624: CYBA:c.58+290C>T (chr16-88650666-G-A) – ACMG Classification: Benign (-20 pts)

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.58+290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 594,852 control chromosomes in the GnomAD database, including 28,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6556 hom., cov: 34)

Exomes 𝑓: 0.30 ( 21540 hom. )

Consequence

CYBA
NM_000101.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.95

Publications

43 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=-0.65).

BP6

Variant 16-88650666-G-A is Benign according to our data. Variant chr16-88650666-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4 link	c.58+290C>T		intron_variant	Intron 1 of 5	ENST00000261623.8	NP_000092.2	P13498B4DT46
CYBA	XM_011522905.4 link	c.58+290C>T		intron_variant	Intron 1 of 5		XP_011521207.1	H3BNP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8 link	c.58+290C>T		intron_variant	Intron 1 of 5	1	NM_000101.4	ENSP00000261623.3		P13498

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43295

AN:

152104

Hom.:

6556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.542

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.256

GnomAD2 exomes

AF:

0.259

AC:

22241

AN:

85832

AF XY:

0.254

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.246

Gnomad EAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.353

Gnomad NFE exome

AF:

0.350

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.296

AC:

131229

AN:

442630

Hom.:

21540

Cov.:

AF XY:

0.285

AC XY:

67719

AN XY:

237846

show subpopulations

African (AFR)

AF:

0.192

AC:

2367

AN:

12312

American (AMR)

AF:

0.259

AC:

5813

AN:

22424

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

3624

AN:

14414

East Asian (EAS)

AF:

0.175

AC:

4927

AN:

28182

South Asian (SAS)

AF:

0.129

AC:

7006

AN:

54470

European-Finnish (FIN)

AF:

0.362

AC:

9702

AN:

26792

Middle Eastern (MID)

AF:

0.237

AC:

839

AN:

3544

European-Non Finnish (NFE)

AF:

0.351

AC:

89849

AN:

255766

Other (OTH)

AF:

0.287

AC:

7102

AN:

24726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

4746

9493

14239

18986

23732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.284

AC:

43301

AN:

152222

Hom.:

6556

Cov.:

AF XY:

0.280

AC XY:

20819

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.194

AC:

8062

AN:

41560

American (AMR)

AF:

0.280

AC:

4279

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

858

AN:

3472

East Asian (EAS)

AF:

0.160

AC:

824

AN:

5166

South Asian (SAS)

AF:

0.127

AC:

615

AN:

4832

European-Finnish (FIN)

AF:

0.343

AC:

3629

AN:

10590

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.352

AC:

23949

AN:

67984

Other (OTH)

AF:

0.254

AC:

537

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1618

3235

4853

6470

8088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.326

Hom.:

13312

Bravo

AF:

0.278

Asia WGS

AF:

0.142

AC:

495

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.1

(source)

DANN

Benign

0.95

PhyloP100

-2.0

PromoterAI

-0.062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

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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