rs3818717

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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. Variant chr17-17803791-T-C is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.423

AC:

106132

AN:

250822

Hom.:

26408

AF XY:

0.425

AC XY:

57689

AN XY:

135794

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 SAS exome

AF:

0.210

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

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.532

Gnomad4 EAS exome

AF:

0.0778

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.583

Gnomad4 OTH exome

AF:

0.485

GnomAD4 genome

AF:

0.416

AC:

63350

AN:

152152

Hom.:

15623

Cov.:

AF XY:

0.407

AC XY:

30254

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.530

Gnomad4 EAS

AF:

0.0772

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.513

Gnomad4 NFE

AF:

0.574

Gnomad4 OTH

AF:

0.431

Alfa

AF:

0.528

Hom.:

27737

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

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 22, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 31, 2018

GeneDx

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

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over