16-88643329-C-T

Variant names:

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.*24G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,467,476 control chromosomes in the GnomAD database, including 184,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17711 hom., cov: 32)

Exomes 𝑓: 0.50 ( 166594 hom. )

Consequence

CYBA
NM_000101.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.788

Publications

93 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=-0.84).

BP6

Variant 16-88643329-C-T is Benign according to our data. Variant chr16-88643329-C-T is described in ClinVar as [Benign]. Clinvar id is 1166946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4 link	c.*24G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000261623.8	NP_000092.2	P13498B4DT46
CYBA	XM_011522905.4 link	c.*1837G>A		3_prime_UTR_variant	Exon 6 of 6		XP_011521207.1	H3BNP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8 link	c.*24G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_000101.4	ENSP00000261623.3		P13498

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

72889

AN:

151662

Hom.:

17707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.490

GnomAD2 exomes

AF:

0.492

AC:

46513

AN:

94542

AF XY:

0.496

show subpopulations

Gnomad AFR exome

AF:

0.438

Gnomad AMR exome

AF:

0.483

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.448

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.502

AC:

660123

AN:

1315698

Hom.:

166594

Cov.:

AF XY:

0.502

AC XY:

324850

AN XY:

646652

show subpopulations

African (AFR)

AF:

0.425

AC:

11208

AN:

26384

American (AMR)

AF:

0.491

AC:

13471

AN:

27444

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

13135

AN:

22636

East Asian (EAS)

AF:

0.473

AC:

15328

AN:

32410

South Asian (SAS)

AF:

0.517

AC:

37649

AN:

72764

European-Finnish (FIN)

AF:

0.459

AC:

18086

AN:

39364

Middle Eastern (MID)

AF:

0.558

AC:

2766

AN:

4954

European-Non Finnish (NFE)

AF:

0.504

AC:

521452

AN:

1035148

Other (OTH)

AF:

0.495

AC:

27028

AN:

54594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

15565

31129

46694

62258

77823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.481

AC:

72937

AN:

151778

Hom.:

17711

Cov.:

AF XY:

0.479

AC XY:

35547

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.425

AC:

17598

AN:

41392

American (AMR)

AF:

0.511

AC:

7818

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

2013

AN:

3470

East Asian (EAS)

AF:

0.407

AC:

2085

AN:

5124

South Asian (SAS)

AF:

0.515

AC:

2475

AN:

4808

European-Finnish (FIN)

AF:

0.451

AC:

4762

AN:

10564

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.510

AC:

34613

AN:

67826

Other (OTH)

AF:

0.488

AC:

1029

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1943

3886

5830

7773

9716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.508

Hom.:

37331

Bravo

AF:

0.480

Asia WGS

AF:

0.454

AC:

1578

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

This variant is associated with the following publications: (PMID: 29132304, 24392120, 10488959, 17684477, 19203534, 19388116, 18324526, 20215507) -

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 10, 2021

Genome-Nilou Lab

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 79% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.64

(source)

DANN

Benign

0.91

PhyloP100

-0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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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16-88643329-C-T

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