rs760275837

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PM4_SupportingBP6BS1

The NM_000101.4(CYBA):c.527_529dupCGG(p.Ala176dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00067 in 1,534,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G177G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 0 hom. )

Consequence

CYBA
NM_000101.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5B:2

Conservation

PhyloP100: 1.94

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: Labcorp Genetics (formerly Invitae), G2P
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 -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000101.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 16-88643411-C-CCCG is Benign according to our data. Variant chr16-88643411-C-CCCG is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 418151.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000427 (65/152070) while in subpopulation NFE AF = 0.000574 (39/67970). AF 95% confidence interval is 0.000431. There are 0 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.527_529dupCGG	p.Ala176dup	conservative_inframe_insertion	Exon 6 of 6	NP_000092.2	P13498

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYBA	ENST00000261623.8	TSL:1 MANE Select	c.527_529dupCGG	p.Ala176dup	conservative_inframe_insertion	Exon 6 of 6	ENSP00000261623.3	P13498
CYBA	ENST00000967613.1		c.575_577dupCGG	p.Ala192dup	conservative_inframe_insertion	Exon 7 of 7	ENSP00000637672.1
CYBA	ENST00000696160.1		c.554_556dupCGG	p.Ala185dup	conservative_inframe_insertion	Exon 7 of 7	ENSP00000512450.1	A0A8Q3WL20

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000574

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000284

AC:

AN:

126554

AF XY:

0.000259

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000838

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000557

Gnomad NFE exome

AF:

0.000613

Gnomad OTH exome

AF:

0.000261

GnomAD4 exome

AF:

0.000697

AC:

963

AN:

1382322

Hom.:

Cov.:

AF XY:

0.000666

AC XY:

454

AN XY:

681880

show subpopulations

African (AFR)

AF:

0.0000993

AC:

AN:

30198

American (AMR)

AF:

0.000142

AC:

AN:

35096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24848

East Asian (EAS)

AF:

0.00

AC:

AN:

34898

South Asian (SAS)

AF:

0.00

AC:

AN:

78502

European-Finnish (FIN)

AF:

0.000921

AC:

AN:

41268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4592

European-Non Finnish (NFE)

AF:

0.000809

AC:

870

AN:

1075506

Other (OTH)

AF:

0.000819

AC:

AN:

57414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

148

198

247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.000427

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

41430

American (AMR)

AF:

0.000327

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000566

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000574

AC:

AN:

67970

Other (OTH)

AF:

0.000956

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000633

Hom.:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (2)

Chronic granulomatous disease (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=84/16

polymorphism

(source)

Splicing

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over