1-183556317-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

autoimmune disease
Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

SMG7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000433.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NCF2	NM_000433.4	MANE Select	c.1469-87A>C	intron	N/A	NP_000424.2
NCF2	NM_001127651.3		c.1469-87A>C	intron	N/A	NP_001121123.1
NCF2	NM_001410895.1		c.1361-87A>C	intron	N/A	NP_001397824.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NCF2	ENST00000367535.8	TSL:1 MANE Select	c.1469-87A>C	intron	N/A	ENSP00000356505.4
NCF2	ENST00000367536.5	TSL:1	c.1469-87A>C	intron	N/A	ENSP00000356506.1
NCF2	ENST00000697330.1		c.1469-87A>C	intron	N/A	ENSP00000513258.1

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

African (AFR)

AF:

0.910

AC:

23448

AN:

25780

American (AMR)

AF:

0.926

AC:

39037

AN:

42156

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

18460

AN:

23470

East Asian (EAS)

AF:

0.999

AC:

37613

AN:

37656

South Asian (SAS)

AF:

0.939

AC:

72320

AN:

77002

European-Finnish (FIN)

AF:

0.904

AC:

46261

AN:

51156

Middle Eastern (MID)

AF:

0.832

AC:

4187

AN:

5034

European-Non Finnish (NFE)

AF:

0.883

AC:

667418

AN:

756024

Other (OTH)

AF:

0.884

AC:

41780

AN:

47260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

5584

11168

16753

22337

27921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12076

24152

36228

48304

60380

<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

AF:

0.894

AC:

136002

AN:

152204

Hom.:

60855

Cov.:

AF XY:

0.896

AC XY:

66675

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.906

AC:

37637

AN:

41520

American (AMR)

AF:

0.893

AC:

13664

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.780

AC:

2707

AN:

3470

East Asian (EAS)

AF:

0.998

AC:

5168

AN:

5178

South Asian (SAS)

AF:

0.948

AC:

4567

AN:

4820

European-Finnish (FIN)

AF:

0.908

AC:

9623

AN:

10600

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.879

AC:

59750

AN:

68004

Other (OTH)

AF:

0.860

AC:

1817

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

729

1458

2188

2917

3646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.874

Hom.:

4649

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Aug 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.99

(source)

DANN

Benign

0.40

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over