22-36868788-A-G

Variant names:

• chr22-36868788-A-G
• rs17811059
• NM_000631.5:c.342+1326A>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.342+1326A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 152,154 control chromosomes in the GnomAD database, including 507 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 0.080 (507 hom., cov: 32)
• Consequence: NCF4 NM_000631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.087 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF4	NM_000631.5	MANE Select	c.342+1326A>G		intron	N/A	NP_000622.2
	NCF4	NM_013416.4		c.342+1326A>G		intron	N/A	NP_038202.2	Q15080-3
	NCF4-AS1	NR_147197.1		n.351+1305T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF4	ENST00000248899.11	TSL:1 MANE Select	c.342+1326A>G		intron	N/A	ENSP00000248899.6	Q15080-1
	NCF4	ENST00000397147.7	TSL:1	c.342+1326A>G		intron	N/A	ENSP00000380334.4	Q15080-3
	NCF4	ENST00000650698.1		c.33+1326A>G		intron	N/A	ENSP00000498381.1	A0A494BZS1

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12112 AN: 152036 Hom.: 502 Cov.: 32

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.0940

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

GnomAD4 genome AF: 0.0796 AC: 12118 AN: 152154 Hom.: 507 Cov.: 32 AF XY: 0.0792 AC XY: 5891 AN XY: 74374

African (AFR) AF: 0.0717 AC: 2977 AN: 41524

American (AMR) AF: 0.0643 AC: 983 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 308 AN: 3470

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5176

South Asian (SAS) AF: 0.0576 AC: 278 AN: 4828

European-Finnish (FIN) AF: 0.108 AC: 1144 AN: 10578

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0889 AC: 6041 AN: 67976

Other (OTH) AF: 0.0925 AC: 195 AN: 2108

Alfa AF: 0.0511 Hom.: 77

Bravo AF: 0.0767

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.015
DANN	Benign	0.51
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17811059; hg19: chr22-37264830;