22-36875639-C-A
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000631.5(NCF4):c.628-14C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,609,904 control chromosomes in the GnomAD database, including 304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 13 hom., cov: 32)
Exomes 𝑓: 0.018 ( 291 hom. )
Consequence
NCF4
NM_000631.5 splice_polypyrimidine_tract, intron
NM_000631.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.657
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 22-36875639-C-A is Benign according to our data. Variant chr22-36875639-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 260305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.012 (1829/152256) while in subpopulation SAS AF= 0.0278 (134/4812). AF 95% confidence interval is 0.024. There are 13 homozygotes in gnomad4. There are 862 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.628-14C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000248899.11 | |||
NCF4 | NM_013416.4 | c.628-14C>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
NCF4 | XM_047441384.1 | c.802-14C>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
NCF4 | XM_047441385.1 | c.772-14C>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCF4 | ENST00000248899.11 | c.628-14C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000631.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0120 AC: 1832AN: 152138Hom.: 13 Cov.: 32
GnomAD3 genomes
AF:
AC:
1832
AN:
152138
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0152 AC: 3762AN: 247390Hom.: 39 AF XY: 0.0164 AC XY: 2202AN XY: 134140
GnomAD3 exomes
AF:
AC:
3762
AN:
247390
Hom.:
AF XY:
AC XY:
2202
AN XY:
134140
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0178 AC: 26013AN: 1457648Hom.: 291 Cov.: 31 AF XY: 0.0184 AC XY: 13313AN XY: 725292
GnomAD4 exome
AF:
AC:
26013
AN:
1457648
Hom.:
Cov.:
31
AF XY:
AC XY:
13313
AN XY:
725292
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0120 AC: 1829AN: 152256Hom.: 13 Cov.: 32 AF XY: 0.0116 AC XY: 862AN XY: 74458
GnomAD4 genome
AF:
AC:
1829
AN:
152256
Hom.:
Cov.:
32
AF XY:
AC XY:
862
AN XY:
74458
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
54
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 11, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at