rs758154907
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_000631.5(NCF4):c.463C>A(p.Arg155=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000018 in 1,611,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
NCF4
NM_000631.5 synonymous
NM_000631.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 6.47
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.2).
BP6
?
Variant 22-36870535-C-A is Benign according to our data. Variant chr22-36870535-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 539174.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.463C>A | p.Arg155= | synonymous_variant | 5/10 | ENST00000248899.11 | |
NCF4 | NM_013416.4 | c.463C>A | p.Arg155= | synonymous_variant | 5/9 | ||
NCF4 | XM_047441384.1 | c.637C>A | p.Arg213= | synonymous_variant | 6/11 | ||
NCF4 | XM_047441385.1 | c.607C>A | p.Arg203= | synonymous_variant | 6/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCF4 | ENST00000248899.11 | c.463C>A | p.Arg155= | synonymous_variant | 5/10 | 1 | NM_000631.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249108Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134866
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1459684Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 726266
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2022 | - - |
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