dbSNP rs17849501: NCF2:p.Ala202Ala (chr1-183573188-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000433.4(NCF2):c.606G>A(p.Ala202Ala) 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:6

Conservation

PhyloP100: -1.21

Publications

31 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 -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 VariationId is 197668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

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	HGVSp	Effect	Exon Rank	Protein
NCF2	NM_000433.4	MANE Select	c.606G>A	p.Ala202Ala	synonymous	Exon 5 of 15	NP_000424.2
NCF2	NM_001127651.3		c.606G>A	p.Ala202Ala	synonymous	Exon 6 of 16	NP_001121123.1
NCF2	NM_001190794.2		c.471G>A	p.Ala157Ala	synonymous	Exon 4 of 14	NP_001177723.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NCF2	ENST00000367535.8	TSL:1 MANE Select	c.606G>A	p.Ala202Ala	synonymous	Exon 5 of 15	ENSP00000356505.4
NCF2	ENST00000367536.5	TSL:1	c.606G>A	p.Ala202Ala	synonymous	Exon 6 of 16	ENSP00000356506.1
NCF2	ENST00000946295.1		c.606G>A	p.Ala202Ala	synonymous	Exon 5 of 16	ENSP00000616354.1

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

GnomAD2 exomes

AF:

0.0343

AC:

8631

AN:

251482

AF XY:

0.0351

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 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

African (AFR)

AF:

0.00848

AC:

284

AN:

33474

American (AMR)

AF:

0.0276

AC:

1236

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0598

AC:

1562

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0157

AC:

1354

AN:

86240

European-Finnish (FIN)

AF:

0.0366

AC:

1954

AN:

53402

Middle Eastern (MID)

AF:

0.0302

AC:

173

AN:

5726

European-Non Finnish (NFE)

AF:

0.0510

AC:

56654

AN:

1111412

Other (OTH)

AF:

0.0446

AC:

2692

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

3383

6766

10149

13532

16915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2090

4180

6270

8360

10450

<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:

0.0353

AC:

5369

AN:

152276

Hom.:

132

Cov.:

AF XY:

0.0346

AC XY:

2579

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00991

AC:

412

AN:

41558

American (AMR)

AF:

0.0396

AC:

606

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0663

AC:

230

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.0124

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0435

AC:

462

AN:

10614

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0501

AC:

3408

AN:

68020

Other (OTH)

AF:

0.0383

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

270

539

809

1078

1348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0468

Hom.:

475

Bravo

AF:

0.0352

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0496

EpiControl

AF:

0.0495

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.1

(source)

DANN

Benign

0.84

PhyloP100

-1.2

Mutation Taster

=98/2

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