ENST00000569359.5:c.*187A>G

Variant names:

• chr16-88645911-T-C
• rs12709102
• ENST00000569359.5:c.*187A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000569359.5(CYBA):​c.*187A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 595,550 control chromosomes in the GnomAD database, including 42,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9329 hom., cov: 32)
  • Exomes 𝑓: 0.38 (33624 hom.)
• Consequence: CYBA ENST00000569359.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.12
• Publications: 32 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=-0.92).
• BP6: Variant 16-88645911-T-C is Benign according to our data. Variant chr16-88645911-T-C is described in ClinVar as Benign. ClinVar VariationId is 1223918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4	c.369+205A>G		intron_variant	Intron 5 of 5	ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.369+205A>G		intron_variant	Intron 5 of 5		XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8	c.369+205A>G		intron_variant	Intron 5 of 5	1	NM_000101.4	ENSP00000261623.3

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50059 AN: 151828 Hom.: 9322 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.379 AC: 168305 AN: 443602 Hom.: 33624 Cov.: 4 AF XY: 0.377 AC XY: 87687 AN XY: 232534

African (AFR) AF: 0.153 AC: 1911 AN: 12530

American (AMR) AF: 0.376 AC: 7530 AN: 20002

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 4213 AN: 13754

East Asian (EAS) AF: 0.201 AC: 6198 AN: 30810

South Asian (SAS) AF: 0.316 AC: 14397 AN: 45616

European-Finnish (FIN) AF: 0.453 AC: 13283 AN: 29318

Middle Eastern (MID) AF: 0.314 AC: 608 AN: 1934

European-Non Finnish (NFE) AF: 0.419 AC: 110520 AN: 263890

Other (OTH) AF: 0.375 AC: 9645 AN: 25748

GnomAD4 genome AF: 0.329 AC: 50064 AN: 151948 Hom.: 9329 Cov.: 32 AF XY: 0.329 AC XY: 24455 AN XY: 74242

African (AFR) AF: 0.152 AC: 6305 AN: 41466

American (AMR) AF: 0.362 AC: 5523 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1251 AN: 5160

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4812

European-Finnish (FIN) AF: 0.452 AC: 4769 AN: 10544

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28385 AN: 67922

Other (OTH) AF: 0.345 AC: 728 AN: 2108

Alfa AF: 0.384 Hom.: 44458

Bravo AF: 0.316

Asia WGS AF: 0.261 AC: 906 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

- -

Mar 03, 2015

GeneDx

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	-0.92
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-3.1
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: rs12709102; hg19: chr16-88712319;