Genetic Variant CYBA:p.Ile188Ile (chr16-88643377-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000101.4(CYBA):c.564C>A(p.Ile188Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000652 in 1,380,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. I188I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

CYBA
NM_000101.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.149

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 16-88643377-G-T is Benign according to our data. Variant chr16-88643377-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1142806.Status of the report is criteria_provided_single_submitter, 1 stars.

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.564C>A	p.Ile188Ile	synonymous	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.564C>A	p.Ile188Ile	synonymous	Exon 6 of 6	ENSP00000261623.3	P13498
CYBA	ENST00000696161.1		c.694C>A	p.Pro232Thr	missense	Exon 6 of 6	ENSP00000512451.1	A0A8Q3WL26
CYBA	ENST00000967613.1		c.612C>A	p.Ile204Ile	synonymous	Exon 7 of 7	ENSP00000637672.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000652

AC:

AN:

1380216

Hom.:

Cov.:

AF XY:

0.00000588

AC XY:

AN XY:

680708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29298

American (AMR)

AF:

0.00

AC:

AN:

34644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24618

East Asian (EAS)

AF:

0.00

AC:

AN:

34364

South Asian (SAS)

AF:

0.00

AC:

AN:

78020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42760

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5180

European-Non Finnish (NFE)

AF:

0.00000838

AC:

AN:

1074020

Other (OTH)

AF:

0.00

AC:

AN:

57312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.35

(source)

DANN

Benign

0.74

PhyloP100

-0.15

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over