Variant 16-88643461-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000101.4(CYBA):c.480G>A(p.Pro160=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,530,872 control chromosomes in the GnomAD database, including 549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 44 hom., cov: 33)

Exomes 𝑓: 0.025 ( 505 hom. )

Consequence

CYBA
NM_000101.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -6.79

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 16-88643461-C-T is Benign according to our data. Variant chr16-88643461-C-T is described in ClinVar as [Benign]. Clinvar id is 284654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88643461-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-6.8 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0216 (3293/152114) while in subpopulation AMR AF= 0.0314 (481/15300). AF 95% confidence interval is 0.0291. There are 44 homozygotes in gnomad4. There are 1617 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBA	NM_000101.4 linkuse as main transcript	c.480G>A	p.Pro160=	synonymous_variant	6/6	ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4 linkuse as main transcript	c.*1705G>A		3_prime_UTR_variant	6/6		XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8 linkuse as main transcript	c.480G>A	p.Pro160=	synonymous_variant	6/6	1	NM_000101.4	ENSP00000261623	P1

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3296

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00541

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.0632

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00934

Gnomad FIN

AF:

0.0274

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0320

GnomAD3 exomes

AF:

0.0231

AC:

2951

AN:

127656

Hom.:

AF XY:

0.0224

AC XY:

1568

AN XY:

70082

show subpopulations

Gnomad AFR exome

AF:

0.00523

Gnomad AMR exome

AF:

0.0213

Gnomad ASJ exome

AF:

0.0605

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.0258

Gnomad NFE exome

AF:

0.0291

Gnomad OTH exome

AF:

0.0345

GnomAD4 exome

AF:

0.0246

AC:

33882

AN:

1378758

Hom.:

505

Cov.:

AF XY:

0.0243

AC XY:

16518

AN XY:

680362

show subpopulations

Gnomad4 AFR exome

AF:

0.00684

Gnomad4 AMR exome

AF:

0.0235

Gnomad4 ASJ exome

AF:

0.0637

Gnomad4 EAS exome

AF:

0.0000285

Gnomad4 SAS exome

AF:

0.0113

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.0256

Gnomad4 OTH exome

AF:

0.0282

GnomAD4 genome

AF:

0.0216

AC:

3293

AN:

152114

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

1617

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00539

Gnomad4 AMR

AF:

0.0314

Gnomad4 ASJ

AF:

0.0632

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00914

Gnomad4 FIN

AF:

0.0274

Gnomad4 NFE

AF:

0.0287

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.0207

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.00786

AC:

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 19, 2015

- -

Chronic granulomatous disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.7

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over