Variant 16-88650978-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000101.4(CYBA):c.36A>G(p.Glu12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,596,232 control chromosomes in the GnomAD database, including 797,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75697 hom., cov: 34)

Exomes 𝑓: 1.0 ( 721466 hom. )

Consequence

CYBA
NM_000101.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.114

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 (BayesDel_noAF=-0.62).

BP6

Variant 16-88650978-T-C is Benign according to our data. Variant chr16-88650978-T-C is described in ClinVar as [Benign]. Clinvar id is 1168658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88650978-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.114 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBA	NM_000101.4 linkuse as main transcript	c.36A>G	p.Glu12=	synonymous_variant	1/6	ENST00000261623.8
CYBA	XM_011522905.4 linkuse as main transcript	c.36A>G	p.Glu12=	synonymous_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBA	ENST00000261623.8 linkuse as main transcript	c.36A>G	p.Glu12=	synonymous_variant	1/6	1	NM_000101.4	P1

Frequencies

GnomAD3 genomes

AF:

0.997

AC:

151738

AN:

152204

Hom.:

75640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.990

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.999

GnomAD3 exomes

AF:

0.999

AC:

215897

AN:

216058

Hom.:

107870

AF XY:

1.00

AC XY:

117996

AN XY:

118054

show subpopulations

Gnomad AFR exome

AF:

0.989

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1443413

AN:

1443910

Hom.:

721466

Cov.:

AF XY:

1.00

AC XY:

716748

AN XY:

716940

show subpopulations

Gnomad4 AFR exome

AF:

0.988

Gnomad4 AMR exome

AF:

0.999

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.999

GnomAD4 genome

AF:

0.997

AC:

151854

AN:

152322

Hom.:

75697

Cov.:

AF XY:

0.997

AC XY:

74258

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.990

Gnomad4 AMR

AF:

0.998

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.999

Alfa

AF:

0.999

Hom.:

26392

Bravo

AF:

0.996

Asia WGS

AF:

0.999

AC:

3472

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -

not specified

Benign:1

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 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Chronic granulomatous disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Jan 11, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

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

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