rs201405375
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_030665.4(RAI1):c.4295C>T(p.Pro1432Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,613,494 control chromosomes in the GnomAD database, including 1 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 Likely benign (★★).
Frequency
Consequence
NM_030665.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAI1 | NM_030665.4 | c.4295C>T | p.Pro1432Leu | missense_variant | 3/6 | ENST00000353383.6 | NP_109590.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAI1 | ENST00000353383.6 | c.4295C>T | p.Pro1432Leu | missense_variant | 3/6 | 1 | NM_030665.4 | ENSP00000323074.4 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000463 AC: 116AN: 250450Hom.: 1 AF XY: 0.000435 AC XY: 59AN XY: 135604
GnomAD4 exome AF: 0.000185 AC: 270AN: 1461144Hom.: 1 Cov.: 37 AF XY: 0.000169 AC XY: 123AN XY: 726884
GnomAD4 genome AF: 0.000223 AC: 34AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74500
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 13, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | RAI1: BP4, BS1 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 08, 2016 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 22, 2019 | This alteration is classified as 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. - |
RAI1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 26, 2022 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Smith-Magenis syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at