rs12933505

Variant names:

• chr16-88646359-A-G
• rs12933505
• NM_000101.4:c.288-162T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-88646359-A-G
• chr16-88646359-A-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.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 NM_000101.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.85
• Publications: 10 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.91).
• BP6: Variant 16-88646359-A-G is Benign according to our data. Variant chr16-88646359-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	NM_000101.4	MANE Select	c.288-162T>C		intron	N/A	NP_000092.2	P13498

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	ENST00000261623.8	TSL:1 MANE Select	c.288-162T>C		intron	N/A	ENSP00000261623.3	P13498
	CYBA	ENST00000569359.5	TSL:1	c.288-162T>C		intron	N/A	ENSP00000456079.1	H3BR52
	CYBA	ENST00000696161.1		c.418-162T>C		intron	N/A	ENSP00000512451.1	A0A8Q3WL26

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

African (AFR) AF: 0.532 AC: 7542 AN: 14188

American (AMR) AF: 0.736 AC: 20014 AN: 27192

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 8754 AN: 15724

East Asian (EAS) AF: 0.863 AC: 26589 AN: 30808

South Asian (SAS) AF: 0.606 AC: 31701 AN: 52354

European-Finnish (FIN) AF: 0.800 AC: 23564 AN: 29444

Middle Eastern (MID) AF: 0.554 AC: 1808 AN: 3266

European-Non Finnish (NFE) AF: 0.646 AC: 185430 AN: 287004

Other (OTH) AF: 0.650 AC: 17851 AN: 27448

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

African (AFR) AF: 0.541 AC: 22382 AN: 41340

American (AMR) AF: 0.720 AC: 10984 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1985 AN: 3466

East Asian (EAS) AF: 0.863 AC: 4441 AN: 5146

South Asian (SAS) AF: 0.620 AC: 2983 AN: 4808

European-Finnish (FIN) AF: 0.817 AC: 8609 AN: 10534

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.661 AC: 44785 AN: 67776

Other (OTH) AF: 0.629 AC: 1325 AN: 2106

Alfa AF: 0.657 Hom.: 53302

Bravo AF: 0.640

Asia WGS AF: 0.710 AC: 2470 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.16
PhyloP100		-2.9
PromoterAI		0.042	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12933505; hg19: chr16-88712767;