rs12933505

Positions:

• chr16-88646359-A-G
• chr16-88646359-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000261623.8(CYBA):​c.288-162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,626 control chromosomes in the GnomAD database, including 32,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32350 hom., cov: 31)
  • Exomes 𝑓: 0.66 (109806 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYBA ENST00000261623.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.85

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=-0.91).
• BP6: Variant 16-88646359-A-G is Benign according to our data. Variant chr16-88646359-A-G is described in ClinVar as [Benign]. Clinvar id is 1234040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBA	NM_000101.4	c.288-162T>C		intron_variant		ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.288-162T>C		intron_variant			XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8	c.288-162T>C		intron_variant		1	NM_000101.4	ENSP00000261623	P1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98211 AN: 151508 Hom.: 32327 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.628

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.663 AC: 323253 AN: 487428 Hom.: 109806 Cov.: 5 AF XY: 0.658 AC XY: 170249 AN XY: 258842

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.736

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.863

Gnomad4 SAS exome AF: 0.606

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.646

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.648 AC: 98273 AN: 151626 Hom.: 32350 Cov.: 31 AF XY: 0.656 AC XY: 48597 AN XY: 74104

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.629

Alfa AF: 0.649 Hom.: 8108

Bravo AF: 0.640

Asia WGS AF: 0.710 AC: 2470 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	Aug 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs12933505; hg19: chr16-88712767;