X-37780087-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000397.4(CYBB):ā€‹c.10T>Cā€‹(p.Trp4Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000896 in 111,617 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000090 ( 0 hom., 0 hem., cov: 22)

Consequence

CYBB
NM_000397.4 missense

Scores

7
8
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.23
Variant links:
Genes affected
CYBB (HGNC:2578): (cytochrome b-245 beta chain) Cytochrome b (-245) is composed of cytochrome b alpha (CYBA) and beta (CYBB) chain. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes. CYBB deficiency is one of five described biochemical defects associated with chronic granulomatous disease (CGD). In this disorder, there is decreased activity of phagocyte NADPH oxidase; neutrophils are able to phagocytize bacteria but cannot kill them in the phagocytic vacuoles. The cause of the killing defect is an inability to increase the cell's respiration and consequent failure to deliver activated oxygen into the phagocytic vacuole. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYBBNM_000397.4 linkc.10T>C p.Trp4Arg missense_variant Exon 1 of 13 ENST00000378588.5 NP_000388.2 P04839A0A0S2Z3S6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYBBENST00000378588.5 linkc.10T>C p.Trp4Arg missense_variant Exon 1 of 13 1 NM_000397.4 ENSP00000367851.4 P04839
ENSG00000250349ENST00000465127.1 linkc.171+354087T>C intron_variant Intron 3 of 8 5 ENSP00000417050.1 B4E171

Frequencies

GnomAD3 genomes
AF:
0.00000896
AC:
1
AN:
111563
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33751
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000378
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000546
AC:
1
AN:
183153
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67673
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 SAS exome
AF:
0.0000524
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
28
GnomAD4 genome
AF:
0.00000896
AC:
1
AN:
111617
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33815
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000380
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.36
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.75
D
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.80
T
M_CAP
Pathogenic
0.79
D
MetaRNN
Uncertain
0.56
D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-6.7
D
REVEL
Pathogenic
0.84
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.011
D
Polyphen
0.71
P
Vest4
0.12
MutPred
0.66
Gain of disorder (P = 0.0058);
MVP
1.0
MPC
1.1
ClinPred
0.79
D
GERP RS
5.4
Varity_R
0.92
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782495755; hg19: chrX-37639340; API