22-36930468-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000395.3(CSF2RB):c.812C>T(p.Ser271Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S271S) has been classified as Likely benign.
Frequency
Consequence
NM_000395.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSF2RB | NM_000395.3 | c.812C>T | p.Ser271Leu | missense_variant | 7/14 | ENST00000403662.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSF2RB | ENST00000403662.8 | c.812C>T | p.Ser271Leu | missense_variant | 7/14 | 5 | NM_000395.3 | P1 | |
CSF2RB | ENST00000406230.5 | c.812C>T | p.Ser271Leu | missense_variant | 6/13 | 1 | |||
CSF2RB | ENST00000421539.1 | c.572C>T | p.Ser191Leu | missense_variant | 6/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251386Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135894
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461420Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 726984
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
Surfactant metabolism dysfunction, pulmonary, 5 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2011 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 29, 2021 | 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. Experimental studies have shown that this variant affects CSF2RB protein function (PMID: 21205713). This variant has been observed in individual(s) with pulmonary alveolar proteinosis (PMID: 21205713). ClinVar contains an entry for this variant (Variation ID: 161978). This variant is present in population databases (rs672601313, ExAC 0.003%). This sequence change replaces serine with leucine at codon 271 of the CSF2RB protein (p.Ser271Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at