rs10854695
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000631.5(NCF4):c.69G>A(p.Ser23Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,613,954 control chromosomes in the GnomAD database, including 2,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.069 ( 938 hom., cov: 31)
Exomes 𝑓: 0.013 ( 1376 hom. )
Consequence
NCF4
NM_000631.5 synonymous
NM_000631.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.406
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 22-36864081-G-A is Benign according to our data. Variant chr22-36864081-G-A is described in ClinVar as [Benign]. Clinvar id is 260306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36864081-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.406 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.69G>A | p.Ser23Ser | synonymous_variant | 2/10 | ENST00000248899.11 | NP_000622.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NCF4 | ENST00000248899.11 | c.69G>A | p.Ser23Ser | synonymous_variant | 2/10 | 1 | NM_000631.5 | ENSP00000248899.6 |
Frequencies
GnomAD3 genomes AF: 0.0687 AC: 10440AN: 151976Hom.: 935 Cov.: 31
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GnomAD3 exomes AF: 0.0412 AC: 10371AN: 251492Hom.: 787 AF XY: 0.0325 AC XY: 4414AN XY: 135922
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GnomAD4 exome AF: 0.0134 AC: 19572AN: 1461860Hom.: 1376 Cov.: 32 AF XY: 0.0121 AC XY: 8788AN XY: 727238
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GnomAD4 genome AF: 0.0688 AC: 10465AN: 152094Hom.: 938 Cov.: 31 AF XY: 0.0681 AC XY: 5063AN XY: 74350
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 16, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
NCF4-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 06, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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