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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
  • Potocki-Lupski syndrome
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030665.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RAI1
NM_030665.4
MANE Select
c.846_872delGCAGCAGCAGCAGCAGCAGCAGCAGCAp.Gln283_Gln291del
disruptive_inframe_deletion
Exon 3 of 6NP_109590.3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RAI1
ENST00000353383.6
TSL:1 MANE Select
c.846_872delGCAGCAGCAGCAGCAGCAGCAGCAGCAp.Gln283_Gln291del
disruptive_inframe_deletion
Exon 3 of 6ENSP00000323074.4Q7Z5J4-1
RAI1
ENST00000918590.1
c.846_872delGCAGCAGCAGCAGCAGCAGCAGCAGCAp.Gln283_Gln291del
disruptive_inframe_deletion
Exon 2 of 5ENSP00000588649.1
RAI1
ENST00000955422.1
c.846_872delGCAGCAGCAGCAGCAGCAGCAGCAGCAp.Gln283_Gln291del
disruptive_inframe_deletion
Exon 3 of 6ENSP00000625481.1

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

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not provided (1)
-
1
-
RAI1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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