Variant rs1049255 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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. Variant chr16-88643329-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CYBA	NM_000101.4 linkuse as main transcript	c.*24G>A		3_prime_UTR_variant	6/6	ENST00000261623.8	NP_000092.2	P13498B4DT46
CYBA	XM_011522905.4 linkuse as main transcript	c.*1837G>A		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 linkuse as main transcript	c.*24G>A		3_prime_UTR_variant	6/6	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

GnomAD3 exomes

AF:

0.492

AC:

46513

AN:

94542

Hom.:

11539

AF XY:

0.496

AC XY:

26486

AN XY:

53380

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 SAS exome

AF:

0.515

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

Gnomad4 AFR exome

AF:

0.425

Gnomad4 AMR exome

AF:

0.491

Gnomad4 ASJ exome

AF:

0.580

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.517

Gnomad4 FIN exome

AF:

0.459

Gnomad4 NFE exome

AF:

0.504

Gnomad4 OTH exome

AF:

0.495

GnomAD4 genome

AF:

0.481

AC:

72937

AN:

151778

Hom.:

17711

Cov.:

AF XY:

0.479

AC XY:

35547

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.425

Gnomad4 AMR

AF:

0.511

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.515

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.514

Hom.:

22979

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 29132304, 24392120, 10488959, 17684477, 19203534, 19388116, 18324526, 20215507) -

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

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 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

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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