rs3180279

Variant names:

• chr16-88644425-C-G
• rs3180279
• NM_000101.4:c.370-854G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-88644425-C-G
• chr16-88644425-C-T

Variant summary

Our verdict is Benign. The variant received -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
• 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: 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261623.8. 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.370-854G>C		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.370-854G>C		intron	N/A	ENSP00000261623.3
	CYBA	ENST00000696162.1		c.*235G>C		3_prime_UTR	Exon 6 of 6	ENSP00000512452.1
	CYBA	ENST00000696161.1		c.500-854G>C		intron	N/A	ENSP00000512451.1

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

African (AFR) AF: 0.449 AC: 18609 AN: 41468

American (AMR) AF: 0.548 AC: 8383 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2035 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3818 AN: 5178

South Asian (SAS) AF: 0.588 AC: 2842 AN: 4832

European-Finnish (FIN) AF: 0.558 AC: 5900 AN: 10576

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34371 AN: 67982

Other (OTH) AF: 0.522 AC: 1102 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.35
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs3180279; hg19: chr16-88710833;