chr16-88643560-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000101.4(CYBA):c.381T>C(p.Arg127Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 1,532,918 control chromosomes in the GnomAD database, including 1,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 74 hom., cov: 33)

Exomes 𝑓: 0.033 ( 955 hom. )

Consequence

CYBA
NM_000101.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.72

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066922307).

BP6

Variant 16-88643560-A-G is Benign according to our data. Variant chr16-88643560-A-G is described in ClinVar as [Benign]. Clinvar id is 255127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88643560-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.72 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0248 (3771/151950) while in subpopulation NFE AF= 0.0385 (2618/67916). AF 95% confidence interval is 0.0373. There are 74 homozygotes in gnomad4. There are 1810 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4 link	c.381T>C	p.Arg127Arg	synonymous_variant	Exon 6 of 6	ENST00000261623.8	NP_000092.2	P13498B4DT46
CYBA	XM_011522905.4 link	c.*1606T>C		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.381T>C	p.Arg127Arg	synonymous_variant	Exon 6 of 6	1	NM_000101.4	ENSP00000261623.3		P13498

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3771

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00593

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0415

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0209

AC:

2715

AN:

130142

Hom.:

AF XY:

0.0197

AC XY:

1405

AN XY:

71382

show subpopulations

Gnomad AFR exome

AF:

0.00422

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.0416

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0223

GnomAD4 exome

AF:

0.0333

AC:

46053

AN:

1380968

Hom.:

955

Cov.:

AF XY:

0.0321

AC XY:

21906

AN XY:

681722

show subpopulations

Gnomad4 AFR exome

AF:

0.00527

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.00143

Gnomad4 FIN exome

AF:

0.0415

Gnomad4 NFE exome

AF:

0.0390

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0248

AC:

3771

AN:

151950

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1810

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.00594

Gnomad4 AMR

AF:

0.0243

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0415

Gnomad4 NFE

AF:

0.0385

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0200

Hom.:

Bravo

AF:

0.0217

TwinsUK

AF:

0.0299

AC:

111

ALSPAC

AF:

0.0371

AC:

143

ESP6500AA

AF:

0.00281

AC:

ESP6500EA

AF:

0.0240

AC:

147

ExAC

AF:

0.00744

AC:

542

Asia WGS

AF:

0.00145

AC:

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 25, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Chronic granulomatous disease

Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.069

DANN

Benign

0.57

FATHMM_MKL

Benign

0.010

MetaRNN

Benign

0.0067

PROVEAN

Pathogenic

-7.0

GERP RS

-8.4

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over