NM_000631.5:c.342+342T>C

Variant names:

• chr22-36867804-T-C
• rs729749
• NM_000631.5:c.342+342T>C

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+342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,104 control chromosomes in the GnomAD database, including 40,436 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 0.73 (40436 hom., cov: 32)
• Consequence: NCF4 NM_000631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 20 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 (NFE) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCF4	NM_000631.5	c.342+342T>C		intron_variant	Intron 4 of 9	ENST00000248899.11	NP_000622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF4	ENST00000248899.11	c.342+342T>C		intron_variant	Intron 4 of 9	1	NM_000631.5	ENSP00000248899.6

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110332 AN: 151986 Hom.: 40408 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.726 AC: 110413 AN: 152104 Hom.: 40436 Cov.: 32 AF XY: 0.724 AC XY: 53842 AN XY: 74366

African (AFR) AF: 0.636 AC: 26384 AN: 41468

American (AMR) AF: 0.719 AC: 10994 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2841 AN: 3468

East Asian (EAS) AF: 0.616 AC: 3175 AN: 5156

South Asian (SAS) AF: 0.707 AC: 3404 AN: 4814

European-Finnish (FIN) AF: 0.771 AC: 8168 AN: 10590

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53033 AN: 67998

Other (OTH) AF: 0.730 AC: 1544 AN: 2116

Alfa AF: 0.761 Hom.: 163948

Bravo AF: 0.716

Asia WGS AF: 0.716 AC: 2490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.094
DANN	Benign	0.51
PhyloP100		-1.9
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: rs729749; hg19: chr22-37263846;