rs11552115

Variant names:

Variant summary

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

The NM_000631.5(NCF4):c.897G>A(p.Ser299Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 1,613,982 control chromosomes in the GnomAD database, including 7,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1462 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5559 hom. )

Consequence

NCF4
NM_000631.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.07

Variant links:

Genes affected

NCF4 (HGNC:7662): (neutrophil cytosolic factor 4) The protein encoded by this gene is a cytosolic regulatory component of the superoxide-producing phagocyte NADPH-oxidase, a multicomponent enzyme system important for host defense. This protein is preferentially expressed in cells of myeloid lineage. It interacts primarily with neutrophil cytosolic factor 2 (NCF2/p67-phox) to form a complex with neutrophil cytosolic factor 1 (NCF1/p47-phox), which further interacts with the small G protein RAC1 and translocates to the membrane upon cell stimulation. This complex then activates flavocytochrome b, the membrane-integrated catalytic core of the enzyme system. The PX domain of this protein can bind phospholipid products of the PI(3) kinase, which suggests its role in PI(3) kinase-mediated signaling events. The phosphorylation of this protein was found to negatively regulate the enzyme activity. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

NCF4 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=-0.9).

BP6

Variant 22-36877700-G-A is Benign according to our data. Variant chr22-36877700-G-A is described in ClinVar as [Benign]. Clinvar id is 260303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36877700-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCF4	NM_000631.5 link	c.897G>A	p.Ser299Ser	synonymous_variant	Exon 10 of 10	ENST00000248899.11	NP_000622.2	Q15080-1
NCF4	XM_047441384.1 link	c.1071G>A	p.Ser357Ser	synonymous_variant	Exon 11 of 11		XP_047297340.1
NCF4	XM_047441385.1 link	c.1041G>A	p.Ser347Ser	synonymous_variant	Exon 11 of 11		XP_047297341.1
NCF4	NM_013416.4 link	c.*95G>A		3_prime_UTR_variant	Exon 9 of 9		NP_038202.2	Q15080-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF4	ENST00000248899.11 link	c.897G>A	p.Ser299Ser	synonymous_variant	Exon 10 of 10	1	NM_000631.5	ENSP00000248899.6		Q15080-1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18189

AN:

152008

Hom.:

1458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.0922

Gnomad EAS

AF:

0.0538

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0572

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0682

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.0963

AC:

24197

AN:

251340

Hom.:

1551

AF XY:

0.0926

AC XY:

12584

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.0877

Gnomad EAS exome

AF:

0.0531

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.0587

Gnomad NFE exome

AF:

0.0663

Gnomad OTH exome

AF:

0.0808

GnomAD4 exome

AF:

0.0790

AC:

115424

AN:

1461856

Hom.:

5559

Cov.:

AF XY:

0.0792

AC XY:

57611

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.0853

Gnomad4 EAS exome

AF:

0.0457

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0584

Gnomad4 NFE exome

AF:

0.0697

Gnomad4 OTH exome

AF:

0.0903

GnomAD4 genome

AF:

0.120

AC:

18228

AN:

152126

Hom.:

1462

Cov.:

AF XY:

0.120

AC XY:

8902

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.223

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.0922

Gnomad4 EAS

AF:

0.0533

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0572

Gnomad4 NFE

AF:

0.0683

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0918

Hom.:

410

Bravo

AF:

0.132

Asia WGS

AF:

0.0850

AC:

296

AN:

3478

EpiCase

AF:

0.0707

EpiControl

AF:

0.0702

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.063

DANN

Benign

0.71

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