X-37780083-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000397.4(CYBB):ā€‹c.6G>Cā€‹(p.Gly2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,208,330 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.00022 ( 0 hom., 5 hem., cov: 22)
Exomes š‘“: 0.000013 ( 0 hom. 3 hem. )

Consequence

CYBB
NM_000397.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.625
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant X-37780083-G-C is Benign according to our data. Variant chrX-37780083-G-C is described in ClinVar as [Benign]. Clinvar id is 788249.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.625 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000215 (24/111572) while in subpopulation AFR AF= 0.000685 (21/30674). AF 95% confidence interval is 0.000458. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYBBNM_000397.4 linkuse as main transcriptc.6G>C p.Gly2= synonymous_variant 1/13 ENST00000378588.5 NP_000388.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYBBENST00000378588.5 linkuse as main transcriptc.6G>C p.Gly2= synonymous_variant 1/131 NM_000397.4 ENSP00000367851 P1

Frequencies

GnomAD3 genomes
AF:
0.000215
AC:
24
AN:
111572
Hom.:
0
Cov.:
22
AF XY:
0.000148
AC XY:
5
AN XY:
33764
show subpopulations
Gnomad AFR
AF:
0.000685
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000286
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000328
AC:
6
AN:
183148
Hom.:
0
AF XY:
0.0000296
AC XY:
2
AN XY:
67658
show subpopulations
Gnomad AFR exome
AF:
0.000380
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000128
AC:
14
AN:
1096758
Hom.:
0
Cov.:
28
AF XY:
0.00000828
AC XY:
3
AN XY:
362182
show subpopulations
Gnomad4 AFR exome
AF:
0.000379
Gnomad4 AMR exome
AF:
0.000114
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000215
AC:
24
AN:
111572
Hom.:
0
Cov.:
22
AF XY:
0.000148
AC XY:
5
AN XY:
33764
show subpopulations
Gnomad4 AFR
AF:
0.000685
Gnomad4 AMR
AF:
0.000286
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000298

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Granulomatous disease, chronic, X-linked Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 11, 2024- -
Chronic granulomatous disease Benign:1
Likely benign, no assertion criteria providedclinical testingNatera, Inc.Apr 16, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
12
DANN
Benign
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs372462475; hg19: chrX-37639336; API