16-88643461-C-T

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.480G>A(p.Pro160Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,530,872 control chromosomes in the GnomAD database, including 549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 44 hom., cov: 33)

Exomes 𝑓: 0.025 ( 505 hom. )

Consequence

CYBA
NM_000101.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.79

Publications

4 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=-0.66).

BP6

Variant 16-88643461-C-T is Benign according to our data. Variant chr16-88643461-C-T is described in ClinVar as Benign. ClinVar VariationId is 284654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.8 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0216 (3293/152114) while in subpopulation AMR AF = 0.0314 (481/15300). AF 95% confidence interval is 0.0291. There are 44 homozygotes in GnomAd4. There are 1617 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 44 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.480G>A	p.Pro160Pro	synonymous	Exon 6 of 6	NP_000092.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CYBA	ENST00000261623.8	TSL:1 MANE Select	c.480G>A	p.Pro160Pro	synonymous	Exon 6 of 6	ENSP00000261623.3
CYBA	ENST00000696161.1		c.610G>A	p.Gly204Ser	missense	Exon 6 of 6	ENSP00000512451.1
CYBA	ENST00000967613.1		c.528G>A	p.Pro176Pro	synonymous	Exon 7 of 7	ENSP00000637672.1

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3296

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00541

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.0632

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00934

Gnomad FIN

AF:

0.0274

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0320

GnomAD2 exomes

AF:

0.0231

AC:

2951

AN:

127656

AF XY:

0.0224

show subpopulations

Gnomad AFR exome

AF:

0.00523

Gnomad AMR exome

AF:

0.0213

Gnomad ASJ exome

AF:

0.0605

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0258

Gnomad NFE exome

AF:

0.0291

Gnomad OTH exome

AF:

0.0345

GnomAD4 exome

AF:

0.0246

AC:

33882

AN:

1378758

Hom.:

505

Cov.:

AF XY:

0.0243

AC XY:

16518

AN XY:

680362

show subpopulations

African (AFR)

AF:

0.00684

AC:

210

AN:

30720

American (AMR)

AF:

0.0235

AC:

830

AN:

35328

Ashkenazi Jewish (ASJ)

AF:

0.0637

AC:

1584

AN:

24874

East Asian (EAS)

AF:

0.0000285

AC:

AN:

35134

South Asian (SAS)

AF:

0.0113

AC:

890

AN:

78774

European-Finnish (FIN)

AF:

0.0272

AC:

1025

AN:

37672

Middle Eastern (MID)

AF:

0.0441

AC:

182

AN:

4124

European-Non Finnish (NFE)

AF:

0.0256

AC:

27547

AN:

1074872

Other (OTH)

AF:

0.0282

AC:

1613

AN:

57260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1882

3764

5646

7528

9410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1020

2040

3060

4080

5100

<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:

0.0216

AC:

3293

AN:

152114

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

1617

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00539

AC:

224

AN:

41534

American (AMR)

AF:

0.0314

AC:

481

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0632

AC:

219

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00914

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0274

AC:

291

AN:

10620

Middle Eastern (MID)

AF:

0.0548

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0287

AC:

1950

AN:

67922

Other (OTH)

AF:

0.0317

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

157

314

472

629

786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0207

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.00786

AC:

AN:

3448

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (2)

not provided (2)

Chronic granulomatous disease (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.7

(source)

DANN

Benign

0.95

PhyloP100

-6.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over