Variant chr1-183556317-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000433.4(NCF2):c.1469-87A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,217,742 control chromosomes in the GnomAD database, including 485,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60855 hom., cov: 31)

Exomes 𝑓: 0.89 ( 424759 hom. )

Consequence

NCF2
NM_000433.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.384

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-183556317-T-G is Benign according to our data. Variant chr1-183556317-T-G is described in ClinVar as [Benign]. Clinvar id is 1226524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.1469-87A>C		intron_variant		ENST00000367535.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCF2	ENST00000367535.8 linkuse as main transcript	c.1469-87A>C		intron_variant		1	NM_000433.4	P1	P19878-1

Frequencies

GnomAD3 genomes

AF:

0.894

AC:

135908

AN:

152086

Hom.:

60816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.907

Gnomad AMI

AF:

0.908

Gnomad AMR

AF:

0.893

Gnomad ASJ

AF:

0.780

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.948

Gnomad FIN

AF:

0.908

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.879

Gnomad OTH

AF:

0.864

GnomAD4 exome

AF:

0.892

AC:

950524

AN:

1065538

Hom.:

424759

AF XY:

0.892

AC XY:

487510

AN XY:

546368

show subpopulations

Gnomad4 AFR exome

AF:

0.910

Gnomad4 AMR exome

AF:

0.926

Gnomad4 ASJ exome

AF:

0.787

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.939

Gnomad4 FIN exome

AF:

0.904

Gnomad4 NFE exome

AF:

0.883

Gnomad4 OTH exome

AF:

0.884

GnomAD4 genome

AF:

0.894

AC:

136002

AN:

152204

Hom.:

60855

Cov.:

AF XY:

0.896

AC XY:

66675

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.906

Gnomad4 AMR

AF:

0.893

Gnomad4 ASJ

AF:

0.780

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.948

Gnomad4 FIN

AF:

0.908

Gnomad4 NFE

AF:

0.879

Gnomad4 OTH

AF:

0.860

Alfa

AF:

0.872

Hom.:

4321

Bravo

AF:

0.903

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 86. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.99

DANN

Benign

0.40

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