rs2296164

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.925-21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,612,180 control chromosomes in the GnomAD database, including 189,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16111 hom., cov: 31)

Exomes 𝑓: 0.48 ( 173749 hom. )

Consequence

NCF2
NM_000433.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.91

Publications

26 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=-0.93).

BP6

Variant 1-183565800-C-T is Benign according to our data. Variant chr1-183565800-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 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	UniProt
NCF2	NM_000433.4	MANE Select	c.925-21G>A	intron	N/A	NP_000424.2	P19878-1
NCF2	NM_001127651.3		c.925-21G>A	intron	N/A	NP_001121123.1	P19878-1
NCF2	NM_001410895.1		c.817-21G>A	intron	N/A	NP_001397824.1	A0A8V8TMB9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCF2	ENST00000367535.8	TSL:1 MANE Select	c.925-21G>A	intron	N/A	ENSP00000356505.4	P19878-1
NCF2	ENST00000367536.5	TSL:1	c.925-21G>A	intron	N/A	ENSP00000356506.1	P19878-1
NCF2	ENST00000946295.1		c.925-21G>A	intron	N/A	ENSP00000616354.1

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69056

AN:

151722

Hom.:

16095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.615

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.461

GnomAD2 exomes

AF:

0.493

AC:

123744

AN:

251004

AF XY:

0.487

show subpopulations

Gnomad AFR exome

AF:

0.354

Gnomad AMR exome

AF:

0.646

Gnomad ASJ exome

AF:

0.392

Gnomad EAS exome

AF:

0.610

Gnomad FIN exome

AF:

0.487

Gnomad NFE exome

AF:

0.467

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.485

AC:

707804

AN:

1460340

Hom.:

173749

Cov.:

AF XY:

0.482

AC XY:

350194

AN XY:

726564

show subpopulations

African (AFR)

AF:

0.348

AC:

11645

AN:

33442

American (AMR)

AF:

0.640

AC:

28583

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

10267

AN:

26116

East Asian (EAS)

AF:

0.625

AC:

24773

AN:

39662

South Asian (SAS)

AF:

0.466

AC:

40151

AN:

86216

European-Finnish (FIN)

AF:

0.480

AC:

25613

AN:

53406

Middle Eastern (MID)

AF:

0.345

AC:

1928

AN:

5588

European-Non Finnish (NFE)

AF:

0.483

AC:

536382

AN:

1110906

Other (OTH)

AF:

0.472

AC:

28462

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

18325

36650

54974

73299

91624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16004

32008

48012

64016

80020

<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:

0.455

AC:

69094

AN:

151840

Hom.:

16111

Cov.:

AF XY:

0.458

AC XY:

33986

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.360

AC:

14891

AN:

41372

American (AMR)

AF:

0.560

AC:

8547

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

1375

AN:

3470

East Asian (EAS)

AF:

0.615

AC:

3174

AN:

5158

South Asian (SAS)

AF:

0.468

AC:

2256

AN:

4816

European-Finnish (FIN)

AF:

0.481

AC:

5066

AN:

10534

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.474

AC:

32197

AN:

67930

Other (OTH)

AF:

0.462

AC:

971

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1885

3770

5655

7540

9425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.463

Hom.:

12516

Bravo

AF:

0.460

Asia WGS

AF:

0.542

AC:

1881

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.014

(source)

DANN

Benign

0.55

PhyloP100

-2.9

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

Computational scores

Splicing

Publications

Other links and lift over