rs3818717

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_030665.4(RAI1):c.5601T>C(p.Ile1867Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,612,858 control chromosomes in the GnomAD database, including 229,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15623 hom., cov: 33)

Exomes 𝑓: 0.52 ( 214154 hom. )

Consequence

RAI1
NM_030665.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.76

Publications

42 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

RAI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.031).

BP6

Variant 17-17803791-T-C is Benign according to our data. Variant chr17-17803791-T-C is described in ClinVar as [Benign]. Clinvar id is 96195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.5601T>C	p.Ile1867Ile	synonymous_variant	Exon 4 of 6	ENST00000353383.6	NP_109590.3	Q7Z5J4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6 link	c.5601T>C	p.Ile1867Ile	synonymous_variant	Exon 4 of 6	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1
RAI1	ENST00000583166.1 link	c.165T>C	p.Ile55Ile	synonymous_variant	Exon 2 of 2	2		ENSP00000463984.1		J3QR08

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63339

AN:

152034

Hom.:

15622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.530

Gnomad EAS

AF:

0.0774

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.433

GnomAD2 exomes

AF:

0.423

AC:

106132

AN:

250822

AF XY:

0.425

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.529

Gnomad EAS exome

AF:

0.0747

Gnomad FIN exome

AF:

0.525

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.523

AC:

764604

AN:

1460706

Hom.:

214154

Cov.:

AF XY:

0.516

AC XY:

374683

AN XY:

726666

show subpopulations

African (AFR)

AF:

0.178

AC:

5951

AN:

33470

American (AMR)

AF:

0.336

AC:

15026

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

13891

AN:

26132

East Asian (EAS)

AF:

0.0778

AC:

3088

AN:

39698

South Asian (SAS)

AF:

0.215

AC:

18549

AN:

86252

European-Finnish (FIN)

AF:

0.528

AC:

27780

AN:

52652

Middle Eastern (MID)

AF:

0.460

AC:

2655

AN:

5766

European-Non Finnish (NFE)

AF:

0.583

AC:

648365

AN:

1111650

Other (OTH)

AF:

0.485

AC:

29299

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

19313

38626

57940

77253

96566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.416

AC:

63350

AN:

152152

Hom.:

15623

Cov.:

AF XY:

0.407

AC XY:

30254

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.196

AC:

8121

AN:

41518

American (AMR)

AF:

0.391

AC:

5973

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

1838

AN:

3470

East Asian (EAS)

AF:

0.0772

AC:

400

AN:

5180

South Asian (SAS)

AF:

0.208

AC:

1003

AN:

4828

European-Finnish (FIN)

AF:

0.513

AC:

5431

AN:

10584

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.574

AC:

39042

AN:

67974

Other (OTH)

AF:

0.431

AC:

910

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1685

3369

5054

6738

8423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.516

Hom.:

33053

Bravo

AF:

0.399

Asia WGS

AF:

0.176

AC:

613

AN:

3478

EpiCase

AF:

0.557

EpiControl

AF:

0.556

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 22, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 31, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Smith-Magenis syndrome

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 03, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 11, 2016

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.9

(source)

DANN

Benign

0.71

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs3818717

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over