chr22-36861077-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000631.5(NCF4):c.-95C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,499,536 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.013 ( 40 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 39 hom. )
Consequence
NCF4
NM_000631.5 5_prime_UTR
NM_000631.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.69
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 22-36861077-C-T is Benign according to our data. Variant chr22-36861077-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1318365.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1919/152226) while in subpopulation AFR AF= 0.0436 (1812/41528). AF 95% confidence interval is 0.042. There are 40 homozygotes in gnomad4. There are 906 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 41 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.-95C>T | 5_prime_UTR_variant | 1/10 | ENST00000248899.11 | ||
NCF4-AS1 | NR_147197.1 | n.351+9016G>A | intron_variant, non_coding_transcript_variant | ||||
NCF4 | NM_013416.4 | c.-95C>T | 5_prime_UTR_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCF4 | ENST00000248899.11 | c.-95C>T | 5_prime_UTR_variant | 1/10 | 1 | NM_000631.5 | P1 | ||
NCF4-AS1 | ENST00000619915.1 | n.349+9016G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0126 AC: 1920AN: 152108Hom.: 41 Cov.: 32
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GnomAD4 exome AF: 0.00127 AC: 1716AN: 1347310Hom.: 39 Cov.: 26 AF XY: 0.00111 AC XY: 743AN XY: 667272
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GnomAD4 genome ? AF: 0.0126 AC: 1919AN: 152226Hom.: 40 Cov.: 32 AF XY: 0.0122 AC XY: 906AN XY: 74430
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at