rs3818717
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_030665.4(RAI1):c.5601T>C(p.Ile1867=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,612,858 control chromosomes in the GnomAD database, including 229,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.42 ( 15623 hom., cov: 33)
Exomes 𝑓: 0.52 ( 214154 hom. )
Consequence
RAI1
NM_030665.4 synonymous
NM_030665.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.76
Genes affected
RAI1 (HGNC:9834): (retinoic acid induced 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It is highly similar to its mouse counterpart and is expressed at high levels mainly in neuronal tissues. The protein encoded by this gene includes a polymorphic polyglutamine tract in the N-terminal domain. Expression of the mouse counterpart in neurons is induced by retinoic acid. This gene is associated with both the severity of the phenotype and the response to medication in schizophrenic patients. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 17-17803791-T-C is Benign according to our data. Variant chr17-17803791-T-C is described in ClinVar as [Benign]. Clinvar id is 96195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17803791-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.76 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAI1 | NM_030665.4 | c.5601T>C | p.Ile1867= | synonymous_variant | 4/6 | ENST00000353383.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAI1 | ENST00000353383.6 | c.5601T>C | p.Ile1867= | synonymous_variant | 4/6 | 1 | NM_030665.4 | P1 | |
RAI1 | ENST00000583166.1 | c.168T>C | p.Ile56= | synonymous_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.417 AC: 63339AN: 152034Hom.: 15622 Cov.: 33
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GnomAD3 exomes AF: 0.423 AC: 106132AN: 250822Hom.: 26408 AF XY: 0.425 AC XY: 57689AN XY: 135794
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GnomAD4 exome AF: 0.523 AC: 764604AN: 1460706Hom.: 214154 Cov.: 51 AF XY: 0.516 AC XY: 374683AN XY: 726666
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GnomAD4 genome ? AF: 0.416 AC: 63350AN: 152152Hom.: 15623 Cov.: 33 AF XY: 0.407 AC XY: 30254AN XY: 74398
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 22, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Smith-Magenis syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 03, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2018 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2016 | 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. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at