chr16-88646323-C-T

Variant names:

• chr16-88646323-C-T
• rs13306294
• NM_000101.4:c.288-126G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000101.4(CYBA):​c.288-126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 661,906 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 35)
  • Exomes 𝑓: 0.0045 (173 hom.)
• Consequence: CYBA NM_000101.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000271 (27/99722) while in subpopulation AMR AF = 0.000504 (5/9928). AF 95% confidence interval is 0.000318. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 173 AR gene

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.288-126G>A		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.288-126G>A		intron	N/A	ENSP00000261623.3
	CYBA	ENST00000569359.5	TSL:1	c.288-126G>A		intron	N/A	ENSP00000456079.1
	CYBA	ENST00000563526.5	TSL:2	n.694G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.000271 AC: 27 AN: 99604 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.000502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000107

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00446 AC: 2507 AN: 562184 Hom.: 173 Cov.: 8 AF XY: 0.00416 AC XY: 1225 AN XY: 294384

African (AFR) AF: 0.00165 AC: 28 AN: 17014

American (AMR) AF: 0.00293 AC: 75 AN: 25596

Ashkenazi Jewish (ASJ) AF: 0.00313 AC: 52 AN: 16620

East Asian (EAS) AF: 0.000100 AC: 3 AN: 30006

South Asian (SAS) AF: 0.00399 AC: 214 AN: 53612

European-Finnish (FIN) AF: 0.000939 AC: 26 AN: 27700

Middle Eastern (MID) AF: 0.00442 AC: 16 AN: 3620

European-Non Finnish (NFE) AF: 0.00555 AC: 1988 AN: 358224

Other (OTH) AF: 0.00352 AC: 105 AN: 29792

GnomAD4 genome AF: 0.000271 AC: 27 AN: 99722 Hom.: 0 Cov.: 35 AF XY: 0.000243 AC XY: 12 AN XY: 49356

African (AFR) AF: 0.000500 AC: 17 AN: 33998

American (AMR) AF: 0.000504 AC: 5 AN: 9928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2164

East Asian (EAS) AF: 0.00 AC: 0 AN: 4308

South Asian (SAS) AF: 0.00 AC: 0 AN: 3272

European-Finnish (FIN) AF: 0.000149 AC: 1 AN: 6692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 198

European-Non Finnish (NFE) AF: 0.000107 AC: 4 AN: 37390

Other (OTH) AF: 0.00 AC: 0 AN: 1302

Alfa AF: 0.182 Hom.: 375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.54
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs13306294; hg19: chr16-88712731; COSMIC: COSV55367799; COSMIC: COSV55367799;