16-88643304-A-C

Variant names:

• chr16-88643304-A-C
• rs7195830
• NM_000101.4:c.*49T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000101.4(CYBA):​c.*49T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000066 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYBA NM_000101.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• Publications: 31 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4	c.*49T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.*1862T>G		3_prime_UTR_variant	Exon 6 of 6		XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8	c.*49T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_000101.4	ENSP00000261623.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000661 AC: 8 AN: 1210730 Hom.: 0 Cov.: 18 AF XY: 0.0000101 AC XY: 6 AN XY: 596186

African (AFR) AF: 0.00 AC: 0 AN: 23798

American (AMR) AF: 0.00 AC: 0 AN: 23308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20350

East Asian (EAS) AF: 0.00 AC: 0 AN: 31300

South Asian (SAS) AF: 0.00 AC: 0 AN: 67136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4654

European-Non Finnish (NFE) AF: 0.00000839 AC: 8 AN: 953498

Other (OTH) AF: 0.00 AC: 0 AN: 50736

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 4169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs7195830; hg19: chr16-88709712;