rs2072706

Variant names:

• chr22-36870937-A-G
• rs2072706
• NM_000631.5:c.470+395A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000631.5(NCF4):​c.470+395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,066 control chromosomes in the GnomAD database, including 32,703 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 0.65 (32703 hom., cov: 31)
• Consequence: NCF4 NM_000631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.65

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCF4	NM_000631.5	c.470+395A>G		intron_variant	Intron 5 of 9	ENST00000248899.11	NP_000622.2
NCF4	NM_013416.4	c.470+395A>G		intron_variant	Intron 5 of 8		NP_038202.2
NCF4	XM_047441384.1	c.644+395A>G		intron_variant	Intron 6 of 10		XP_047297340.1
NCF4	XM_047441385.1	c.614+395A>G		intron_variant	Intron 6 of 10		XP_047297341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF4	ENST00000248899.11	c.470+395A>G		intron_variant	Intron 5 of 9	1	NM_000631.5	ENSP00000248899.6

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99425 AN: 151948 Hom.: 32675 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.654 AC: 99497 AN: 152066 Hom.: 32703 Cov.: 31 AF XY: 0.657 AC XY: 48819 AN XY: 74344

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.652

Alfa AF: 0.670 Hom.: 4247

Bravo AF: 0.645

Asia WGS AF: 0.674 AC: 2343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.027
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs2072706; hg19: chr22-37266979;