1-183573188-C-T

Position:

chr1-183573188-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000433.4(NCF2):c.606G>A(p.Ala202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,613,450 control chromosomes in the GnomAD database, including 1,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 132 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1674 hom. )

Consequence

NCF2
NM_000433.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.21

Variant links:

Genes affected

NCF2 (HGNC:7661): (neutrophil cytosolic factor 2) This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein NADPH oxidase complex found in neutrophils. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome. Mutations in this gene, as well as in other NADPH oxidase subunits, can result in chronic granulomatous disease, a disease that causes recurrent infections by catalase-positive organisms. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]

NCF2 links:

SMG7 (HGNC:16792): (SMG7 nonsense mediated mRNA decay factor) This gene encodes a protein that is essential for nonsense-mediated mRNA decay (NMD); a process whereby transcripts with premature termination codons are targeted for rapid degradation by a mRNA decay complex. The mRNA decay complex consists, in part, of this protein along with proteins SMG5 and UPF1. The N-terminal domain of this protein is thought to mediate its association with SMG5 or UPF1 while the C-terminal domain interacts with the mRNA decay complex. This protein may therefore couple changes in UPF1 phosphorylation state to the degradation of NMD-candidate transcripts. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

SMG7 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=-0.65).

BP6

Variant 1-183573188-C-T is Benign according to our data. Variant chr1-183573188-C-T is described in ClinVar as [Benign]. Clinvar id is 197668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-183573188-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.21 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCF2	NM_000433.4 linkuse as main transcript	c.606G>A	p.Ala202=	synonymous_variant	5/15	ENST00000367535.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCF2	ENST00000367535.8 linkuse as main transcript	c.606G>A	p.Ala202=	synonymous_variant	5/15	1	NM_000433.4	P1	P19878-1

Frequencies

GnomAD3 genomes

AF:

0.0353

AC:

5373

AN:

152158

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00994

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0397

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0435

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0501

Gnomad OTH

AF:

0.0387

GnomAD3 exomes

AF:

0.0343

AC:

8631

AN:

251482

Hom.:

203

AF XY:

0.0351

AC XY:

4769

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00867

Gnomad AMR exome

AF:

0.0255

Gnomad ASJ exome

AF:

0.0594

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.0361

Gnomad NFE exome

AF:

0.0486

Gnomad OTH exome

AF:

0.0428

GnomAD4 exome

AF:

0.0451

AC:

65910

AN:

1461174

Hom.:

1674

Cov.:

AF XY:

0.0443

AC XY:

32225

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.00848

Gnomad4 AMR exome

AF:

0.0276

Gnomad4 ASJ exome

AF:

0.0598

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.0366

Gnomad4 NFE exome

AF:

0.0510

Gnomad4 OTH exome

AF:

0.0446

GnomAD4 genome

AF:

0.0353

AC:

5369

AN:

152276

Hom.:

132

Cov.:

AF XY:

0.0346

AC XY:

2579

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00991

Gnomad4 AMR

AF:

0.0396

Gnomad4 ASJ

AF:

0.0663

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.0435

Gnomad4 NFE

AF:

0.0501

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.0479

Hom.:

350

Bravo

AF:

0.0352

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0496

EpiControl

AF:

0.0495

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 05, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

This variant is associated with the following publications: (PMID: 24163247) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.1

DANN

Benign

0.84

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

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