X-37805187-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000397.4(CYBB):c.1314+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,203,163 control chromosomes in the GnomAD database, including 466 homozygotes. There are 2,592 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 233 hom., 1232 hem., cov: 23)

Exomes 𝑓: 0.0047 ( 233 hom. 1360 hem. )

Consequence

CYBB
NM_000397.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.678

Publications

1 publications found

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]

CYBB Gene-Disease associations (from GenCC):

granulomatous disease, chronic, X-linked
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
chronic granulomatous disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency
Inheritance: XL, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

CYBB links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-37805187-C-T is Benign according to our data. Variant chrX-37805187-C-T is described in ClinVar as Benign. ClinVar VariationId is 35968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBB	NM_000397.4 link	c.1314+19C>T		intron_variant	Intron 10 of 12	ENST00000378588.5	NP_000388.2
CYBB	XM_047441855.1 link	c.1008+19C>T		intron_variant	Intron 9 of 11		XP_047297811.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CYBB	ENST00000378588.5 link	c.1314+19C>T	intron_variant	Intron 10 of 12	1	NM_000397.4	ENSP00000367851.4
ENSG00000250349	ENST00000465127.1 link	c.171+379187C>T	intron_variant	Intron 3 of 8	5		ENSP00000417050.1
CYBB	ENST00000696171.1 link	c.1218+19C>T	intron_variant	Intron 9 of 11			ENSP00000512462.1
CYBB	ENST00000696170.1 link	n.*823+19C>T	intron_variant	Intron 9 of 11			ENSP00000512461.1

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

4594

AN:

112010

Hom.:

233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.000737

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.0318

GnomAD2 exomes

AF:

0.0119

AC:

2146

AN:

179935

AF XY:

0.00767

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.00823

Gnomad ASJ exome

AF:

0.000537

Gnomad EAS exome

AF:

0.000362

Gnomad FIN exome

AF:

0.0000672

Gnomad NFE exome

AF:

0.000511

Gnomad OTH exome

AF:

0.00493

GnomAD4 exome

AF:

0.00474

AC:

5170

AN:

1091099

Hom.:

233

Cov.:

AF XY:

0.00381

AC XY:

1360

AN XY:

357127

show subpopulations

African (AFR)

AF:

0.149

AC:

3902

AN:

26258

American (AMR)

AF:

0.00921

AC:

323

AN:

35068

Ashkenazi Jewish (ASJ)

AF:

0.000673

AC:

AN:

19314

East Asian (EAS)

AF:

0.000166

AC:

AN:

30167

South Asian (SAS)

AF:

0.000390

AC:

AN:

53856

European-Finnish (FIN)

AF:

0.0000252

AC:

AN:

39722

Middle Eastern (MID)

AF:

0.00727

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.000457

AC:

382

AN:

836732

Other (OTH)

AF:

0.0108

AC:

493

AN:

45857

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

182

363

545

726

908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<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

AF:

0.0411

AC:

4602

AN:

112064

Hom.:

233

Cov.:

AF XY:

0.0359

AC XY:

1232

AN XY:

34288

show subpopulations

African (AFR)

AF:

0.140

AC:

4307

AN:

30743

American (AMR)

AF:

0.0191

AC:

203

AN:

10635

Ashkenazi Jewish (ASJ)

AF:

0.000378

AC:

AN:

2648

East Asian (EAS)

AF:

0.000282

AC:

AN:

3547

South Asian (SAS)

AF:

0.000739

AC:

AN:

2707

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6133

Middle Eastern (MID)

AF:

0.0185

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

53223

Other (OTH)

AF:

0.0314

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

153

306

459

612

765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.0483

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Granulomatous disease, chronic, X-linked

Benign:2

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing;curation

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.24

(source)

DANN

Benign

0.60

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over