rs549244691
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_030665.4(RAI1):c.1850C>A(p.Ala617Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000108 in 1,613,136 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 2 hom. )
Consequence
RAI1
NM_030665.4 missense
NM_030665.4 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 4.02
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.018631965).
BP6
?
Variant 17-17794798-C-A is Benign according to our data. Variant chr17-17794798-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 196546.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000116 (169/1460832) while in subpopulation SAS AF= 0.00168 (145/86256). AF 95% confidence interval is 0.00146. There are 2 homozygotes in gnomad4_exome. There are 113 alleles in male gnomad4_exome subpopulation. Median coverage is 94. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAI1 | NM_030665.4 | c.1850C>A | p.Ala617Asp | missense_variant | 3/6 | ENST00000353383.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAI1 | ENST00000353383.6 | c.1850C>A | p.Ala617Asp | missense_variant | 3/6 | 1 | NM_030665.4 | P1 | |
RAI1 | ENST00000395774.1 | c.1850C>A | p.Ala617Asp | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152186Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000268 AC: 67AN: 249646Hom.: 2 AF XY: 0.000354 AC XY: 48AN XY: 135500
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GnomAD4 exome AF: 0.000116 AC: 169AN: 1460832Hom.: 2 Cov.: 94 AF XY: 0.000155 AC XY: 113AN XY: 726748
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74466
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 22, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 23, 2014 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 07, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;.
REVEL
Benign
Sift
Pathogenic
D;D;.
Sift4G
Uncertain
D;D;.
Polyphen
D;.;.
Vest4
MutPred
Gain of disorder (P = 0.0975);Gain of disorder (P = 0.0975);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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