dbSNP rs1049254: CYBA:p.Val174Gly (chr16-88643420-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000101.4(CYBA):c.521T>G(p.Val174Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000362 in 1,380,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V174A) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CYBA
NM_000101.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Publications

51 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 (MetaRNN=0.04502055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4 link	c.521T>G	p.Val174Gly	missense_variant	Exon 6 of 6	ENST00000261623.8	NP_000092.2	P13498B4DT46
CYBA	XM_011522905.4 link	c.*1746T>G		3_prime_UTR_variant	Exon 6 of 6		XP_011521207.1	H3BNP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8 link	c.521T>G	p.Val174Gly	missense_variant	Exon 6 of 6	1	NM_000101.4	ENSP00000261623.3		P13498

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

125396

AF XY:

0.0000145

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000221

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000362

AC:

AN:

1380052

Hom.:

Cov.:

AF XY:

0.00000588

AC XY:

AN XY:

680748

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30140

American (AMR)

AF:

0.00

AC:

AN:

34916

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24784

East Asian (EAS)

AF:

0.00

AC:

AN:

34840

South Asian (SAS)

AF:

0.00

AC:

AN:

78368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4438

European-Non Finnish (NFE)

AF:

0.00000372

AC:

AN:

1074304

Other (OTH)

AF:

0.0000174

AC:

AN:

57314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.70

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.27

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.089

M_CAP

Benign

0.011

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.0

PhyloP100

-1.9

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.48

REVEL

Benign

0.23

Sift

Benign

0.21

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.046

MutPred

0.38

Loss of stability (P = 0.0246);

MVP

0.27

MPC

0.22

ClinPred

0.057

GERP RS

-7.9

Varity_R

0.036

gMVP

0.45

Mutation Taster

=100/0

polymorphism

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over