chr16-88647125-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000101.4(CYBA):c.179A>C(p.Lys60Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 1,611,518 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K60M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0043 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 34 hom. )

Consequence

CYBA
NM_000101.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.04

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 (MetaRNN=0.004710138).

BP6

Variant 16-88647125-T-G is Benign according to our data. Variant chr16-88647125-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 252465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00432 (658/152254) while in subpopulation AMR AF = 0.00988 (151/15290). AF 95% confidence interval is 0.00859. There are 4 homozygotes in GnomAd4. There are 332 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	NM_000101.4	MANE Select	c.179A>C	p.Lys60Thr	missense	Exon 3 of 6	NP_000092.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CYBA	ENST00000261623.8	TSL:1 MANE Select	c.179A>C	p.Lys60Thr	missense	Exon 3 of 6	ENSP00000261623.3
CYBA	ENST00000569359.5	TSL:1	c.179A>C	p.Lys60Thr	missense	Exon 3 of 5	ENSP00000456079.1
CYBA	ENST00000696161.1		c.179A>C	p.Lys60Thr	missense	Exon 3 of 6	ENSP00000512451.1

Frequencies

GnomAD3 genomes

AF:

0.00431

AC:

656

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00989

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00601

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00390

AC:

961

AN:

246468

AF XY:

0.00373

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00596

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000306

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00628

GnomAD4 exome

AF:

0.00568

AC:

8288

AN:

1459264

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

4061

AN XY:

725960

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

33472

American (AMR)

AF:

0.00598

AC:

267

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.000766

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.000847

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.000489

AC:

AN:

51170

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00674

AC:

7490

AN:

1111798

Other (OTH)

AF:

0.00568

AC:

343

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

412

824

1237

1649

2061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.00432

AC:

658

AN:

152254

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

332

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

41550

American (AMR)

AF:

0.00988

AC:

151

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00603

AC:

410

AN:

67998

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00524

Hom.:

Bravo

AF:

0.00487

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00364

AC:

441

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00742

EpiControl

AF:

0.00819

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CYBA: BP4, BS2

Jan 19, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 10910929, 27048830, 29454792, 20167518)

not specified

Benign:2

Sep 11, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 20, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CYBA-related disorder

Benign:1

Feb 25, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.25

CADD

Benign

0.21

(source)

DANN

Uncertain

0.98

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

M_CAP

Benign

0.016

MetaRNN

Benign

0.0047

PhyloP100

-1.0

PROVEAN

Benign

-2.0

MVP

0.085

ClinPred

0.0047

GERP RS

-5.2

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

3.2

Varity_R

0.054

Mutation Taster

=96/4

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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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