rs199991273
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000760.4(CSF3R):c.722C>T(p.Ala241Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,611,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A241A) has been classified as Likely benign.
Frequency
Consequence
NM_000760.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CSF3R | NM_000760.4 | c.722C>T | p.Ala241Val | missense_variant | 7/17 | ENST00000373106.6 | NP_000751.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CSF3R | ENST00000373106.6 | c.722C>T | p.Ala241Val | missense_variant | 7/17 | 1 | NM_000760.4 | ENSP00000362198.2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000775 AC: 19AN: 245226Hom.: 0 AF XY: 0.0000972 AC XY: 13AN XY: 133812
GnomAD4 exome AF: 0.0000521 AC: 76AN: 1458970Hom.: 0 Cov.: 32 AF XY: 0.0000483 AC XY: 35AN XY: 725362
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74452
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 10, 2016 | - - |
Autosomal recessive severe congenital neutropenia due to CSF3R deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 11, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 434842). This variant has not been reported in the literature in individuals affected with CSF3R-related conditions. This variant is present in population databases (rs199991273, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 241 of the CSF3R protein (p.Ala241Val). - |
CSF3R-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 23, 2024 | The CSF3R c.722C>T variant is predicted to result in the amino acid substitution p.Ala241Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at