rs2072711
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000631.5(NCF4):c.627+88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,152,614 control chromosomes in the GnomAD database, including 402,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.86 ( 56218 hom., cov: 27)
Exomes 𝑓: 0.83 ( 346151 hom. )
Consequence
NCF4
NM_000631.5 intron
NM_000631.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.829
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 22-36872513-A-G is Benign according to our data. Variant chr22-36872513-A-G is described in ClinVar as [Benign]. Clinvar id is 1289546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.627+88A>G | intron_variant | ENST00000248899.11 | |||
NCF4 | NM_013416.4 | c.627+88A>G | intron_variant | ||||
NCF4 | XM_047441384.1 | c.801+88A>G | intron_variant | ||||
NCF4 | XM_047441385.1 | c.771+88A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCF4 | ENST00000248899.11 | c.627+88A>G | intron_variant | 1 | NM_000631.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.861 AC: 129932AN: 150942Hom.: 56151 Cov.: 27
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GnomAD4 exome AF: 0.831 AC: 831906AN: 1001554Hom.: 346151 AF XY: 0.830 AC XY: 426989AN XY: 514530
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GnomAD4 genome ? AF: 0.861 AC: 130057AN: 151060Hom.: 56218 Cov.: 27 AF XY: 0.860 AC XY: 63414AN XY: 73766
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at