chr16-88646805-C-G

Position:

• chr16-88646805-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000101.4(CYBA):​c.237G>C​(p.Leu79Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 1,613,928 control chromosomes in the GnomAD database, including 795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (409 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (386 hom.)
• Consequence: CYBA NM_000101.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.00300

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016738176).
• BP6: Variant 16-88646805-C-G is Benign according to our data. Variant chr16-88646805-C-G is described in ClinVar as [Benign]. Clinvar id is 255126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88646805-C-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.003 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBA	NM_000101.4	c.237G>C	p.Leu79Leu	synonymous_variant	4/6	ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.237G>C	p.Leu79Leu	synonymous_variant	4/6		XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8	c.237G>C	p.Leu79Leu	synonymous_variant	4/6	1	NM_000101.4	ENSP00000261623.3

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6174 AN: 152078 Hom.: 407 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0102 AC: 2562 AN: 251036 Hom.: 160 AF XY: 0.00763 AC XY: 1036 AN XY: 135838

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.00654

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00402 AC: 5874 AN: 1461732 Hom.: 386 Cov.: 31 AF XY: 0.00339 AC XY: 2463 AN XY: 727192

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.00693

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000710

Gnomad4 OTH exome AF: 0.00911

GnomAD4 genome AF: 0.0406 AC: 6182 AN: 152196 Hom.: 409 Cov.: 33 AF XY: 0.0392 AC XY: 2915 AN XY: 74408

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.00444 Hom.: 19

Bravo AF: 0.0460

ESP6500AA AF: 0.143 AC: 627

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.0126 AC: 1536

Asia WGS AF: 0.00779 AC: 28 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Chronic granulomatous disease Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.8
DANN	Benign	0.87
FATHMM_MKL	Benign	0.54	D
MetaRNN	Benign	0.0017	T
PROVEAN	Benign	-1.7	N
GERP RS		0.68
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

LitVar

Other links and lift over

dbSNP: rs2228472; hg19: chr16-88713213;