Genetic Variant NM_000101.4:c.*49T>C (chr16-88643304-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000101.4(CYBA):c.*49T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,358,570 control chromosomes in the GnomAD database, including 268,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36858 hom., cov: 31)

Exomes 𝑓: 0.62 ( 231144 hom. )

Consequence

CYBA
NM_000101.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.744

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=-0.9).

BP6

Variant 16-88643304-A-G is Benign according to our data. Variant chr16-88643304-A-G is described in ClinVar as [Benign]. Clinvar id is 1172927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4 link	c.*49T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000261623.8	NP_000092.2	P13498B4DT46
CYBA	XM_011522905.4 link	c.*1862T>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 link	c.*49T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_000101.4	ENSP00000261623.3		P13498

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

104570

AN:

151652

Hom.:

36808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.836

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.650

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.761

Gnomad SAS

AF:

0.711

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.736

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.678

GnomAD3 exomes

AF:

0.618

AC:

44774

AN:

72504

Hom.:

14052

AF XY:

0.620

AC XY:

25486

AN XY:

41116

show subpopulations

Gnomad AFR exome

AF:

0.818

Gnomad AMR exome

AF:

0.581

Gnomad ASJ exome

AF:

0.669

Gnomad EAS exome

AF:

0.721

Gnomad SAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.626

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.616

GnomAD4 exome

AF:

0.616

AC:

742928

AN:

1206800

Hom.:

231144

Cov.:

AF XY:

0.617

AC XY:

366682

AN XY:

594336

show subpopulations

Gnomad4 AFR exome

AF:

0.841

Gnomad4 AMR exome

AF:

0.604

Gnomad4 ASJ exome

AF:

0.693

Gnomad4 EAS exome

AF:

0.797

Gnomad4 SAS exome

AF:

0.693

Gnomad4 FIN exome

AF:

0.644

Gnomad4 NFE exome

AF:

0.595

Gnomad4 OTH exome

AF:

0.633

GnomAD4 genome

AF:

0.690

AC:

104673

AN:

151770

Hom.:

36858

Cov.:

AF XY:

0.694

AC XY:

51469

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.836

Gnomad4 AMR

AF:

0.650

Gnomad4 ASJ

AF:

0.692

Gnomad4 EAS

AF:

0.760

Gnomad4 SAS

AF:

0.710

Gnomad4 FIN

AF:

0.672

Gnomad4 NFE

AF:

0.607

Gnomad4 OTH

AF:

0.677

Alfa

AF:

0.619

Hom.:

4169

Bravo

AF:

0.693

Asia WGS

AF:

0.748

AC:

2604

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

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

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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