rs12709102

Positions:

• chr16-88645911-T-C
• chr16-88645911-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BP6: Variant 16-88645911-T-C is Benign according to our data. Variant chr16-88645911-T-C is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
CYBA	NM_000101.4	c.369+205A>G		intron_variant		ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.369+205A>G		intron_variant			XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8	c.369+205A>G		intron_variant		1	NM_000101.4	ENSP00000261623	P1

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

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.453

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.375

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

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.345

Alfa AF: 0.392 Hom.: 19331

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.39

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: rs12709102; hg19: chr16-88712319;