16-88643304-A-G

Variant names:

• chr16-88643304-A-G
• rs7195830
• NM_000101.4:c.*49T>C

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.744
• Publications: 31 publications found

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 Gene-Disease associations (from GenCC):

• granulomatous disease, chronic, autosomal recessive, cytochrome b-negative

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• chronic granulomatous disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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	c.*49T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.*1862T>C		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	ENST00000261623.8	c.*49T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_000101.4	ENSP00000261623.3

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

GnomAD2 exomes AF: 0.618 AC: 44774 AN: 72504 AF XY: 0.620

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 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

African (AFR) AF: 0.841 AC: 19964 AN: 23738

American (AMR) AF: 0.604 AC: 13972 AN: 23134

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 14047 AN: 20272

East Asian (EAS) AF: 0.797 AC: 24900 AN: 31250

South Asian (SAS) AF: 0.693 AC: 46361 AN: 66938

European-Finnish (FIN) AF: 0.644 AC: 23114 AN: 35888

Middle Eastern (MID) AF: 0.693 AC: 3210 AN: 4632

European-Non Finnish (NFE) AF: 0.595 AC: 565368 AN: 950394

Other (OTH) AF: 0.633 AC: 31992 AN: 50554

GnomAD4 genome AF: 0.690 AC: 104673 AN: 151770 Hom.: 36858 Cov.: 31 AF XY: 0.694 AC XY: 51469 AN XY: 74170

African (AFR) AF: 0.836 AC: 34653 AN: 41438

American (AMR) AF: 0.650 AC: 9931 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2399 AN: 3466

East Asian (EAS) AF: 0.760 AC: 3886 AN: 5110

South Asian (SAS) AF: 0.710 AC: 3417 AN: 4810

European-Finnish (FIN) AF: 0.672 AC: 7083 AN: 10548

Middle Eastern (MID) AF: 0.743 AC: 217 AN: 292

European-Non Finnish (NFE) AF: 0.607 AC: 41167 AN: 67822

Other (OTH) AF: 0.677 AC: 1424 AN: 2104

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

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
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7195830; hg19: chr16-88709712;