Genetic Variant NCF4:p.Ser118Asn (chr22-36870425-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000631.5(NCF4):c.353G>A(p.Ser118Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

NCF4
NM_000631.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.37

Publications

2 publications found

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:

NCF4-AS1 (HGNC:40393): (NCF4 antisense RNA 1)

NCF4-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25904354).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000631.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NCF4	NM_000631.5	MANE Select	c.353G>A	p.Ser118Asn	missense	Exon 5 of 10	NP_000622.2
NCF4	NM_013416.4		c.353G>A	p.Ser118Asn	missense	Exon 5 of 9	NP_038202.2
NCF4-AS1	NR_147197.1		n.19C>T		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NCF4	ENST00000248899.11	TSL:1 MANE Select	c.353G>A	p.Ser118Asn	missense	Exon 5 of 10	ENSP00000248899.6
NCF4	ENST00000397147.7	TSL:1	c.353G>A	p.Ser118Asn	missense	Exon 5 of 9	ENSP00000380334.4
NCF4	ENST00000650698.1		c.44G>A	p.Ser15Asn	missense	Exon 5 of 10	ENSP00000498381.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.019

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.076

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

M_CAP

Benign

0.025

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

6.4

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.28

REVEL

Benign

0.10

Sift

Benign

0.28

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.27

MutPred

0.43

Loss of ubiquitination at K114 (P = 0.1113)

MVP

0.86

MPC

0.42

ClinPred

0.76

GERP RS

4.7

Varity_R

0.11

gMVP

0.23

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over