Genetic Variant CYBA:p.Gln3Lys (chr16-88651007-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000101.4(CYBA):c.7C>A(p.Gln3Lys) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q3H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYBA
NM_000101.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Publications

0 publications found

Variant links:

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

CYBA links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26180202).

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.7C>A	p.Gln3Lys	missense	Exon 1 of 6	NP_000092.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CYBA	ENST00000261623.8	TSL:1 MANE Select	c.7C>A	p.Gln3Lys	missense	Exon 1 of 6	ENSP00000261623.3
CYBA	ENST00000569359.5	TSL:1	c.7C>A	p.Gln3Lys	missense	Exon 1 of 5	ENSP00000456079.1
CYBA	ENST00000696161.1		c.7C>A	p.Gln3Lys	missense	Exon 1 of 6	ENSP00000512451.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1443828

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717154

African (AFR)

AF:

0.00

AC:

AN:

32970

American (AMR)

AF:

0.00

AC:

AN:

43136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25742

East Asian (EAS)

AF:

0.00

AC:

AN:

38558

South Asian (SAS)

AF:

0.00

AC:

AN:

84046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5488

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105250

Other (OTH)

AF:

0.00

AC:

AN:

59610

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.6

PhyloP100

1.8

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.0

REVEL

Benign

0.20

Sift

Benign

0.62

Sift4G

Benign

0.99

Polyphen

0.011

Vest4

0.13

MutPred

0.58

Gain of methylation at Q3 (P = 0.0135)

MVP

0.73

MPC

0.31

ClinPred

0.27

GERP RS

2.8

PromoterAI

-0.19

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.2

Varity_R

0.24

gMVP

0.62

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over