16-88650666-G-A

Variant names:

• chr16-88650666-G-A
• rs3794624
• NM_000101.4:c.58+290C>T

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.58+290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 594,852 control chromosomes in the GnomAD database, including 28,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6556 hom., cov: 34)
  • Exomes 𝑓: 0.30 (21540 hom.)
• Consequence: CYBA NM_000101.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.95
• Publications: 43 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=-0.65).
• BP6: Variant 16-88650666-G-A is Benign according to our data. Variant chr16-88650666-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000101.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	NM_000101.4	MANE Select	c.58+290C>T		intron	N/A	NP_000092.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	ENST00000261623.8	TSL:1 MANE Select	c.58+290C>T		intron	N/A	ENSP00000261623.3
	CYBA	ENST00000569359.5	TSL:1	c.58+290C>T		intron	N/A	ENSP00000456079.1
	CYBA	ENST00000696161.1		c.58+290C>T		intron	N/A	ENSP00000512451.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43295 AN: 152104 Hom.: 6556 Cov.: 34

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.256

GnomAD2 exomes AF: 0.259 AC: 22241 AN: 85832 AF XY: 0.254

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.261

Gnomad ASJ exome AF: 0.246

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.353

Gnomad NFE exome AF: 0.350

Gnomad OTH exome AF: 0.278

GnomAD4 exome AF: 0.296 AC: 131229 AN: 442630 Hom.: 21540 Cov.: 2 AF XY: 0.285 AC XY: 67719 AN XY: 237846

African (AFR) AF: 0.192 AC: 2367 AN: 12312

American (AMR) AF: 0.259 AC: 5813 AN: 22424

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 3624 AN: 14414

East Asian (EAS) AF: 0.175 AC: 4927 AN: 28182

South Asian (SAS) AF: 0.129 AC: 7006 AN: 54470

European-Finnish (FIN) AF: 0.362 AC: 9702 AN: 26792

Middle Eastern (MID) AF: 0.237 AC: 839 AN: 3544

European-Non Finnish (NFE) AF: 0.351 AC: 89849 AN: 255766

Other (OTH) AF: 0.287 AC: 7102 AN: 24726

GnomAD4 genome AF: 0.284 AC: 43301 AN: 152222 Hom.: 6556 Cov.: 34 AF XY: 0.280 AC XY: 20819 AN XY: 74416

African (AFR) AF: 0.194 AC: 8062 AN: 41560

American (AMR) AF: 0.280 AC: 4279 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 858 AN: 3472

East Asian (EAS) AF: 0.160 AC: 824 AN: 5166

South Asian (SAS) AF: 0.127 AC: 615 AN: 4832

European-Finnish (FIN) AF: 0.343 AC: 3629 AN: 10590

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23949 AN: 67984

Other (OTH) AF: 0.254 AC: 537 AN: 2114

Alfa AF: 0.326 Hom.: 13312

Bravo AF: 0.278

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Aug 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.1
DANN	Benign	0.95
PhyloP100		-2.0
PromoterAI		-0.062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs3794624; hg19: chr16-88717074; COSMIC: COSV55368387; COSMIC: COSV55368387;