17-17794723-G-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBS1BS2

The NM_030665.4(RAI1):​c.1775G>C​(p.Arg592Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000182 in 1,611,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

RAI1
NM_030665.4 missense

Scores

3
10
6

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.32
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.32425493).
BP6
Variant 17-17794723-G-C is Benign according to our data. Variant chr17-17794723-G-C is described in ClinVar as [Benign]. Clinvar id is 1601163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000158 (24/152260) while in subpopulation NFE AF= 0.000264 (18/68054). AF 95% confidence interval is 0.000171. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAI1NM_030665.4 linkc.1775G>C p.Arg592Pro missense_variant 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.1775G>C p.Arg592Pro missense_variant Exon 3 of 6 1 NM_030665.4 ENSP00000323074.4 Q7Z5J4-1
RAI1ENST00000395774.1 linkc.1775G>C p.Arg592Pro missense_variant Exon 2 of 2 2 ENSP00000379120.1 A8MXE8

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152260
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000264
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000146
AC:
36
AN:
246130
Hom.:
0
AF XY:
0.000142
AC XY:
19
AN XY:
134224
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000278
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
AF:
0.000184
AC:
269
AN:
1459048
Hom.:
0
Cov.:
94
AF XY:
0.000180
AC XY:
131
AN XY:
725978
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000231
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152260
Hom.:
0
Cov.:
33
AF XY:
0.000108
AC XY:
8
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000264
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.000106
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000466
AC:
4
ExAC
AF:
0.000132
AC:
16
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Oct 03, 2024
Ambry Genetics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

RAI1-related disorder Benign:1
Jul 12, 2021
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
Jan 27, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.23
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
T;.;.
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.85
D;D;T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Uncertain
0.33
D
MutationAssessor
Benign
0.97
L;.;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.7
N;D;.
REVEL
Uncertain
0.30
Sift
Pathogenic
0.0
D;D;.
Sift4G
Uncertain
0.038
D;D;.
Polyphen
0.99
D;.;.
Vest4
0.72
MVP
0.92
MPC
1.1
ClinPred
0.13
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.49
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141808855; hg19: chr17-17698037; API