rs2072711

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.627+88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,152,614 control chromosomes in the GnomAD database, including 402,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 56218 hom., cov: 27)

Exomes 𝑓: 0.83 ( 346151 hom. )

Consequence

NCF4
NM_000631.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.829

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=-0.92).

BP6

Variant 22-36872513-A-G is Benign according to our data. Variant chr22-36872513-A-G is described in ClinVar as [Benign]. Clinvar id is 1289546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NCF4	NM_000631.5 link	c.627+88A>G	intron_variant	Intron 7 of 9	ENST00000248899.11	NP_000622.2	Q15080-1
NCF4	NM_013416.4 link	c.627+88A>G	intron_variant	Intron 7 of 8		NP_038202.2	Q15080-3
NCF4	XM_047441384.1 link	c.801+88A>G	intron_variant	Intron 8 of 10		XP_047297340.1
NCF4	XM_047441385.1 link	c.771+88A>G	intron_variant	Intron 8 of 10		XP_047297341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF4	ENST00000248899.11 link	c.627+88A>G		intron_variant	Intron 7 of 9	1	NM_000631.5	ENSP00000248899.6		Q15080-1

Frequencies

GnomAD3 genomes

AF:

0.861

AC:

129932

AN:

150942

Hom.:

56151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.945

Gnomad AMI

AF:

0.765

Gnomad AMR

AF:

0.867

Gnomad ASJ

AF:

0.863

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.798

Gnomad FIN

AF:

0.834

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.860

GnomAD4 exome

AF:

0.831

AC:

831906

AN:

1001554

Hom.:

346151

AF XY:

0.830

AC XY:

426989

AN XY:

514530

show subpopulations

Gnomad4 AFR exome

AF:

0.949

Gnomad4 AMR exome

AF:

0.862

Gnomad4 ASJ exome

AF:

0.857

Gnomad4 EAS exome

AF:

0.711

Gnomad4 SAS exome

AF:

0.818

Gnomad4 FIN exome

AF:

0.845

Gnomad4 NFE exome

AF:

0.830

Gnomad4 OTH exome

AF:

0.842

GnomAD4 genome

AF:

0.861

AC:

130057

AN:

151060

Hom.:

56218

Cov.:

AF XY:

0.860

AC XY:

63414

AN XY:

73766

show subpopulations

Gnomad4 AFR

AF:

0.945

Gnomad4 AMR

AF:

0.867

Gnomad4 ASJ

AF:

0.863

Gnomad4 EAS

AF:

0.677

Gnomad4 SAS

AF:

0.798

Gnomad4 FIN

AF:

0.834

Gnomad4 NFE

AF:

0.832

Gnomad4 OTH

AF:

0.860

Alfa

AF:

0.834

Hom.:

107068

Bravo

AF:

0.866

Asia WGS

AF:

0.798

AC:

2772

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 10, 2019

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

- -

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 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.53

DANN

Benign

0.57

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