16-88643329-C-T

Variant names:

• chr16-88643329-C-T
• rs1049255
• NM_000101.4:c.*24G>A

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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.788

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=-0.84).
• 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 rank	MANE	Protein	UniProt
CYBA	NM_000101.4	c.*24G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.*1837G>A		3_prime_UTR_variant	Exon 6 of 6		XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623	c.*24G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_000101.4	ENSP00000261623.3

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72889 AN: 151662 Hom.: 17707 Cov.: 32

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

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.: 24 AF XY: 0.502 AC XY: 324850 AN XY: 646652

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.: 32 AF XY: 0.479 AC XY: 35547 AN XY: 74166

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

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

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

Jun 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 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

Other links and lift over

dbSNP: rs1049255; hg19: chr16-88709737; COSMIC: COSV54918632; COSMIC: COSV54918632;