GeneBe

rs371983878

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_030665.4(RAI1):​c.846_872delGCAGCAGCAGCAGCAGCAGCAGCAGCA​(p.Gln283_Gln291del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000391 in 1,278,812 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q282Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

RAI1
NM_030665.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 4.86

Publications

8 publications found
Variant links:
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]
RAI1 Gene-Disease associations (from GenCC):
  • Smith-Magenis syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
  • Potocki-Lupski syndrome
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_030665.4
BS2
High AC in GnomAdExome4 at 50 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAI1NM_030665.4 linkc.846_872delGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln283_Gln291del disruptive_inframe_deletion Exon 3 of 6 ENST00000353383.6 NP_109590.3 Q7Z5J4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAI1ENST00000353383.6 linkc.846_872delGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln283_Gln291del disruptive_inframe_deletion Exon 3 of 6 1 NM_030665.4 ENSP00000323074.4 Q7Z5J4-1
RAI1ENST00000395774.1 linkc.846_872delGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln283_Gln291del disruptive_inframe_deletion Exon 2 of 2 2 ENSP00000379120.1 A8MXE8

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.0000391
AC:
50
AN:
1278812
Hom.:
0
AF XY:
0.0000411
AC XY:
26
AN XY:
632490
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28608
American (AMR)
AF:
0.00
AC:
0
AN:
31712
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23378
East Asian (EAS)
AF:
0.0000537
AC:
1
AN:
18624
South Asian (SAS)
AF:
0.0000179
AC:
1
AN:
55806
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
46186
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4866
European-Non Finnish (NFE)
AF:
0.0000442
AC:
45
AN:
1017670
Other (OTH)
AF:
0.0000577
AC:
3
AN:
51962
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.548
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0
Alfa
AF:
0.00
Hom.:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

RAI1-related disorder Uncertain:1
Sep 28, 2024
PreventionGenetics, part of Exact Sciences
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:clinical testing

The RAI1 c.846_872del27 variant is predicted to result in an in-frame deletion (p.Gln283_Gln291del). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

not provided Uncertain:1
Jan 19, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant, c.846_872del, results in the deletion of 9 amino acid(s) of the RAI1 protein (p.Gln283_Gln291del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAI1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.9
Mutation Taster
=135/65
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs371983878; hg19: chr17-17697093; API