chr22-36864559-A-G

Variant names:

• chr22-36864559-A-G
• rs909484
• NM_000631.5:c.118-360A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000631.5(NCF4):​c.118-360A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,146 control chromosomes in the GnomAD database, including 57,454 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (57454 hom., cov: 31)
• Consequence: NCF4 NM_000631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF4	NM_000631.5	MANE Select	c.118-360A>G		intron	N/A	NP_000622.2
	NCF4	NM_013416.4		c.118-360A>G		intron	N/A	NP_038202.2
	NCF4-AS1	NR_147197.1		n.351+5534T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF4	ENST00000248899.11	TSL:1 MANE Select	c.118-360A>G		intron	N/A	ENSP00000248899.6
	NCF4	ENST00000397147.7	TSL:1	c.118-360A>G		intron	N/A	ENSP00000380334.4
	NCF4	ENST00000650698.1		c.-192-360A>G		intron	N/A	ENSP00000498381.1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131783 AN: 152028 Hom.: 57394 Cov.: 31

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.860

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.867 AC: 131903 AN: 152146 Hom.: 57454 Cov.: 31 AF XY: 0.865 AC XY: 64334 AN XY: 74368

African (AFR) AF: 0.958 AC: 39758 AN: 41498

American (AMR) AF: 0.872 AC: 13323 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2982 AN: 3470

East Asian (EAS) AF: 0.789 AC: 4073 AN: 5160

South Asian (SAS) AF: 0.807 AC: 3897 AN: 4828

European-Finnish (FIN) AF: 0.823 AC: 8713 AN: 10582

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56362 AN: 68006

Other (OTH) AF: 0.859 AC: 1816 AN: 2114

Alfa AF: 0.834 Hom.: 33075

Bravo AF: 0.874

Asia WGS AF: 0.850 AC: 2957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.98
DANN	Benign	0.25
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs909484; hg19: chr22-37260601;