rs150054973
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 3P and 9B. PM1PP2BP4_StrongBP6BS2
The NM_002880.4(RAF1):c.853A>G(p.Ser285Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 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). Synonymous variant affecting the same amino acid position (i.e. S285S) has been classified as Likely benign.
Frequency
Consequence
NM_002880.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAF1 | NM_002880.4 | c.853A>G | p.Ser285Gly | missense_variant | 8/17 | ENST00000251849.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAF1 | ENST00000251849.9 | c.853A>G | p.Ser285Gly | missense_variant | 8/17 | 1 | NM_002880.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251420Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135894
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727240
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74498
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2019 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 263589; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function - |
Noonan syndrome Benign:1
Likely benign, no assertion criteria provided | clinical testing | Service de Génétique Moléculaire, Hôpital Robert Debré | - | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
RASopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at