chr16-88643420-A-G

Position:

chr16-88643420-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000101.4(CYBA):c.521T>C(p.Val174Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,530,710 control chromosomes in the GnomAD database, including 302,624 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36615 hom., cov: 34)

Exomes 𝑓: 0.62 ( 266009 hom. )

Consequence

CYBA
NM_000101.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -1.85

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.0484614E-7).

BP6

Variant 16-88643420-A-G is Benign according to our data. Variant chr16-88643420-A-G is described in ClinVar as [Benign]. Clinvar id is 198042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88643420-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBA	NM_000101.4 linkuse as main transcript	c.521T>C	p.Val174Ala	missense_variant	6/6	ENST00000261623.8	NP_000092.2	P13498B4DT46
CYBA	XM_011522905.4 linkuse as main transcript	c.*1746T>C		3_prime_UTR_variant	6/6		XP_011521207.1	H3BNP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8 linkuse as main transcript	c.521T>C	p.Val174Ala	missense_variant	6/6	1	NM_000101.4	ENSP00000261623.3		P13498

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104313

AN:

151816

Hom.:

36568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.831

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.606

Gnomad OTH

AF:

0.676

GnomAD3 exomes

AF:

0.648

AC:

81217

AN:

125396

Hom.:

26674

AF XY:

0.650

AC XY:

44764

AN XY:

68916

show subpopulations

Gnomad AFR exome

AF:

0.820

Gnomad AMR exome

AF:

0.609

Gnomad ASJ exome

AF:

0.702

Gnomad EAS exome

AF:

0.741

Gnomad SAS exome

AF:

0.694

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.600

Gnomad OTH exome

AF:

0.637

GnomAD4 exome

AF:

0.619

AC:

853140

AN:

1378782

Hom.:

266009

Cov.:

AF XY:

0.620

AC XY:

421618

AN XY:

680068

show subpopulations

Gnomad4 AFR exome

AF:

0.836

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.699

Gnomad4 EAS exome

AF:

0.796

Gnomad4 SAS exome

AF:

0.696

Gnomad4 FIN exome

AF:

0.645

Gnomad4 NFE exome

AF:

0.597

Gnomad4 OTH exome

AF:

0.636

GnomAD4 genome

AF:

0.687

AC:

104409

AN:

151928

Hom.:

36615

Cov.:

AF XY:

0.691

AC XY:

51337

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.831

Gnomad4 AMR

AF:

0.646

Gnomad4 ASJ

AF:

0.692

Gnomad4 EAS

AF:

0.759

Gnomad4 SAS

AF:

0.708

Gnomad4 FIN

AF:

0.668

Gnomad4 NFE

AF:

0.606

Gnomad4 OTH

AF:

0.675

Alfa

AF:

0.642

Hom.:

6360

Bravo

AF:

0.691

TwinsUK

AF:

0.593

AC:

2197

ALSPAC

AF:

0.594

AC:

2288

ESP6500AA

AF:

0.821

AC:

1815

ESP6500EA

AF:

0.628

AC:

3364

ExAC

AF:

0.505

AC:

26874

Asia WGS

AF:

0.743

AC:

2576

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 15, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 81. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jan 22, 2024	- -

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -

Chronic granulomatous disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.029

DANN

Benign

0.32

DEOGEN2

Benign

0.23

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.12

MetaRNN

Benign

8.0e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.4

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.22

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.025

MPC

0.20

ClinPred

0.0029

GERP RS

-7.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.017

gMVP

0.41

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

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