1-36466626-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000760.4(CSF3R):c.2242G>A(p.Asp748Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,032 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 (★).
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 | UniProt |
---|---|---|---|---|---|---|---|
CSF3R | NM_000760.4 | c.2242G>A | p.Asp748Asn | missense_variant | 17/17 | ENST00000373106.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSF3R | ENST00000373106.6 | c.2242G>A | p.Asp748Asn | missense_variant | 17/17 | 1 | NM_000760.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251052Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135710
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461720Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727140
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74486
ClinVar
Submissions by phenotype
Autosomal recessive severe congenital neutropenia due to CSF3R deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 748 of the CSF3R protein (p.Asp748Asn). This variant is present in population databases (rs147017250, gnomAD 0.02%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CSF3R protein function. ClinVar contains an entry for this variant (Variation ID: 582331). This variant has not been reported in the literature in individuals affected with CSF3R-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at