rs759302795
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000760.4(CSF3R):c.799del(p.Glu267SerfsTer61) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CSF3R
NM_000760.4 frameshift
NM_000760.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.22
Genes affected
CSF3R (HGNC:2439): (colony stimulating factor 3 receptor) The protein encoded by this gene is the receptor for colony stimulating factor 3, a cytokine that controls the production, differentiation, and function of granulocytes. The encoded protein, which is a member of the family of cytokine receptors, may also function in some cell surface adhesion or recognition processes. Alternatively spliced transcript variants have been described. Mutations in this gene are a cause of Kostmann syndrome, also known as severe congenital neutropenia. [provided by RefSeq, Aug 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-36472560-TC-T is Pathogenic according to our data. Variant chr1-36472560-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 542856.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSF3R | NM_000760.4 | c.799del | p.Glu267SerfsTer61 | frameshift_variant | 7/17 | ENST00000373106.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSF3R | ENST00000373106.6 | c.799del | p.Glu267SerfsTer61 | frameshift_variant | 7/17 | 1 | NM_000760.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1
AN:
152186
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: 0.00000802 AC: 2AN: 249308Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135410
GnomAD3 exomes
AF:
AC:
2
AN:
249308
Hom.:
AF XY:
AC XY:
0
AN XY:
135410
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 Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727238
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1461860
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727238
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: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
GnomAD4 genome
?
AF:
AC:
1
AN:
152186
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74358
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive severe congenital neutropenia due to CSF3R deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CSF3R are known to be pathogenic (PMID: 24753537, 26324699). This variant has not been reported in the literature in individuals with CSF3R-related disease. This variant is present in population databases (rs759302795, ExAC 0.01%). This sequence change creates a premature translational stop signal (p.Glu267Serfs*61) in the CSF3R gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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