rs4782393

Positions:

Variant summary

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

The NM_000101.4(CYBA):c.203+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,606,018 control chromosomes in the GnomAD database, including 201,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15338 hom., cov: 33)

Exomes 𝑓: 0.50 ( 185765 hom. )

Consequence

CYBA
NM_000101.4 splice_region, intron

Scores

Splicing: ADA: 0.00001193

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: -3.29

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 (BayesDel_noAF=-0.91).

BP6

Variant 16-88647093-A-G is Benign according to our data. Variant chr16-88647093-A-G is described in ClinVar as [Benign]. Clinvar id is 196207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88647093-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBA	NM_000101.4 link	c.203+8T>C		splice_region_variant, intron_variant		ENST00000261623.8	NP_000092.2	P13498B4DT46
CYBA	XM_011522905.4 link	c.203+8T>C		splice_region_variant, intron_variant			XP_011521207.1	H3BNP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8 link	c.203+8T>C		splice_region_variant, intron_variant		1	NM_000101.4	ENSP00000261623.3		P13498

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66881

AN:

151974

Hom.:

15322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.436

GnomAD3 exomes

AF:

0.471

AC:

113926

AN:

241700

Hom.:

27931

AF XY:

0.471

AC XY:

61919

AN XY:

131448

show subpopulations

Gnomad AFR exome

AF:

0.306

Gnomad AMR exome

AF:

0.545

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.459

Gnomad FIN exome

AF:

0.526

Gnomad NFE exome

AF:

0.510

Gnomad OTH exome

AF:

0.464

GnomAD4 exome

AF:

0.500

AC:

727537

AN:

1453926

Hom.:

185765

Cov.:

AF XY:

0.499

AC XY:

361289

AN XY:

723468

show subpopulations

Gnomad4 AFR exome

AF:

0.301

Gnomad4 AMR exome

AF:

0.536

Gnomad4 ASJ exome

AF:

0.401

Gnomad4 EAS exome

AF:

0.211

Gnomad4 SAS exome

AF:

0.461

Gnomad4 FIN exome

AF:

0.530

Gnomad4 NFE exome

AF:

0.521

Gnomad4 OTH exome

AF:

0.477

GnomAD4 genome

AF:

0.440

AC:

66918

AN:

152092

Hom.:

15338

Cov.:

AF XY:

0.438

AC XY:

32557

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.491

Gnomad4 ASJ

AF:

0.414

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.448

Gnomad4 FIN

AF:

0.519

Gnomad4 NFE

AF:

0.511

Gnomad4 OTH

AF:

0.438

Alfa

AF:

0.471

Hom.:

3212

Bravo

AF:

0.432

Asia WGS

AF:

0.339

AC:

1180

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 12, 2015	- -
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 74% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -

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

Chronic granulomatous disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.59

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

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