rs34898721
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_030665.4(RAI1):c.1279C>T(p.Leu427=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,613,462 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 2 hom. )
Consequence
RAI1
NM_030665.4 synonymous
NM_030665.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.98
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 17-17794227-C-T is Benign according to our data. Variant chr17-17794227-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 211999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17794227-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.98 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00104 (159/152358) while in subpopulation NFE AF= 0.00175 (119/68036). AF 95% confidence interval is 0.00149. There are 0 homozygotes in gnomad4. There are 65 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 159 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAI1 | NM_030665.4 | c.1279C>T | p.Leu427= | synonymous_variant | 3/6 | ENST00000353383.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAI1 | ENST00000353383.6 | c.1279C>T | p.Leu427= | synonymous_variant | 3/6 | 1 | NM_030665.4 | P1 | |
RAI1 | ENST00000395774.1 | c.1279C>T | p.Leu427= | synonymous_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00104 AC: 159AN: 152240Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000975 AC: 244AN: 250378Hom.: 0 AF XY: 0.00106 AC XY: 143AN XY: 135538
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GnomAD4 exome AF: 0.00105 AC: 1536AN: 1461104Hom.: 2 Cov.: 94 AF XY: 0.00107 AC XY: 777AN XY: 726850
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GnomAD4 genome ? AF: 0.00104 AC: 159AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.000872 AC XY: 65AN XY: 74512
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | RAI1: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 14, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 29, 2016 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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