16-88643304-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.744

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]

ACMG classification

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/exons	MANE	UniProt
CYBA	NM_000101.4	c.*49T>C		3_prime_UTR_variant	6/6	ENST00000261623.8
CYBA	XM_011522905.4	c.*1862T>C		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBA	ENST00000261623.8	c.*49T>C		3_prime_UTR_variant	6/6	1	NM_000101.4	P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104570 AN: 151652 Hom.: 36808 Cov.: 31

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

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.: 18 AF XY: 0.617 AC XY: 366682 AN XY: 594336

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.: 31 AF XY: 0.694 AC XY: 51469 AN XY: 74170

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 81. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

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

Other links and lift over

dbSNP: rs7195830; hg19: chr16-88709712;