rs2072708

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000631.5(NCF4):c.528+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,554,170 control chromosomes in the GnomAD database, including 400,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33492 hom., cov: 34)

Exomes 𝑓: 0.72 ( 366906 hom. )

Consequence

NCF4
NM_000631.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.59

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 22-36871725-A-G is Benign according to our data. Variant chr22-36871725-A-G is described in ClinVar as [Benign]. Clinvar id is 198201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36871725-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NCF4	NM_000631.5 link	c.528+16A>G	intron_variant	Intron 6 of 9	ENST00000248899.11	NP_000622.2	Q15080-1
NCF4	NM_013416.4 link	c.528+16A>G	intron_variant	Intron 6 of 8		NP_038202.2	Q15080-3
NCF4	XM_047441384.1 link	c.702+16A>G	intron_variant	Intron 7 of 10		XP_047297340.1
NCF4	XM_047441385.1 link	c.672+16A>G	intron_variant	Intron 7 of 10		XP_047297341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF4	ENST00000248899.11 link	c.528+16A>G		intron_variant	Intron 6 of 9	1	NM_000631.5	ENSP00000248899.6		Q15080-1

Frequencies

GnomAD3 genomes

AF:

0.650

AC:

98810

AN:

152054

Hom.:

33476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.751

Gnomad ASJ

AF:

0.784

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.717

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.664

GnomAD3 exomes

AF:

0.718

AC:

115428

AN:

160718

Hom.:

41860

AF XY:

0.723

AC XY:

61355

AN XY:

84850

show subpopulations

Gnomad AFR exome

AF:

0.422

Gnomad AMR exome

AF:

0.786

Gnomad ASJ exome

AF:

0.783

Gnomad EAS exome

AF:

0.657

Gnomad SAS exome

AF:

0.752

Gnomad FIN exome

AF:

0.726

Gnomad NFE exome

AF:

0.724

Gnomad OTH exome

AF:

0.710

GnomAD4 exome

AF:

0.721

AC:

1011328

AN:

1401998

Hom.:

366906

Cov.:

AF XY:

0.723

AC XY:

500226

AN XY:

691898

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.781

Gnomad4 ASJ exome

AF:

0.778

Gnomad4 EAS exome

AF:

0.709

Gnomad4 SAS exome

AF:

0.747

Gnomad4 FIN exome

AF:

0.734

Gnomad4 NFE exome

AF:

0.726

Gnomad4 OTH exome

AF:

0.713

GnomAD4 genome

AF:

0.650

AC:

98855

AN:

152172

Hom.:

33492

Cov.:

AF XY:

0.653

AC XY:

48554

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.437

Gnomad4 AMR

AF:

0.751

Gnomad4 ASJ

AF:

0.784

Gnomad4 EAS

AF:

0.676

Gnomad4 SAS

AF:

0.737

Gnomad4 FIN

AF:

0.717

Gnomad4 NFE

AF:

0.731

Gnomad4 OTH

AF:

0.666

Alfa

AF:

0.698

Hom.:

6902

Bravo

AF:

0.639

Asia WGS

AF:

0.728

AC:

2531

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

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 96% of patients studied by a panel of primary immunodeficiencies. Number of patients: 91. Only high quality variants are reported. -

Apr 14, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Aug 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.39

DANN

Benign

0.071

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