rs139332126
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000760.4(CSF3R):āc.447G>Cā(p.Glu149Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,614,236 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E149K) has been classified as Uncertain significance.
Frequency
Consequence
NM_000760.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSF3R | NM_000760.4 | c.447G>C | p.Glu149Asp | missense_variant | 5/17 | ENST00000373106.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSF3R | ENST00000373106.6 | c.447G>C | p.Glu149Asp | missense_variant | 5/17 | 1 | NM_000760.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00294 AC: 448AN: 152238Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00294 AC: 738AN: 251422Hom.: 0 AF XY: 0.00315 AC XY: 428AN XY: 135888
GnomAD4 exome AF: 0.00454 AC: 6637AN: 1461880Hom.: 32 Cov.: 31 AF XY: 0.00439 AC XY: 3190AN XY: 727244
GnomAD4 genome ? AF: 0.00294 AC: 448AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.00246 AC XY: 183AN XY: 74498
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 22, 2021 | Identified in a patient with Shwachman-Diamond syndrome, but it is not clear if the variant occurred as a germline or somatic variant (Klimiankou et al., 2019); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33108454, 30891028) - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2020 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 14, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Aug 15, 2017 | BS1, BP4; This alteration has an allele frequency that is greater than expected for the associated disease, and is predicted to be tolerated by multiple functional prediction tools. - |
Autosomal recessive severe congenital neutropenia due to CSF3R deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
CSF3R-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at