chr16-88644425-C-G

Position:

• chr16-88644425-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000261623.8(CYBA):​c.370-854G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,112 control chromosomes in the GnomAD database, including 20,052 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 0.51 (20052 hom., cov: 33)
• Consequence: CYBA ENST00000261623.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBA	NM_000101.4	c.370-854G>C		intron_variant		ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.*741G>C		3_prime_UTR_variant	6/6		XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8	c.370-854G>C		intron_variant		1	NM_000101.4	ENSP00000261623	P1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77555 AN: 151994 Hom.: 20044 Cov.: 33

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.523

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.510 AC: 77605 AN: 152112 Hom.: 20052 Cov.: 33 AF XY: 0.517 AC XY: 38469 AN XY: 74340

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.522

Alfa AF: 0.501 Hom.: 2109

Bravo AF: 0.507

Asia WGS AF: 0.649 AC: 2260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.35

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: rs3180279; hg19: chr16-88710833;