rs4925112

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030665.4(RAI1):c.4311T>C(p.Pro1437Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 1,612,960 control chromosomes in the GnomAD database, including 5,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1534 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3553 hom. )

Consequence

RAI1
NM_030665.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.11

Publications

14 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 17-17797259-T-C is Benign according to our data. Variant chr17-17797259-T-C is described in ClinVar as Benign. ClinVar VariationId is 96190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.4311T>C	p.Pro1437Pro	synonymous_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
RAI1	ENST00000353383.6 link	c.4311T>C	p.Pro1437Pro	synonymous_variant	Exon 3 of 6	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16435

AN:

151972

Hom.:

1522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0566

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.00483

Gnomad SAS

AF:

0.0248

Gnomad FIN

AF:

0.0748

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0596

Gnomad OTH

AF:

0.0943

GnomAD2 exomes

AF:

0.0605

AC:

15096

AN:

249448

AF XY:

0.0568

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.0357

Gnomad ASJ exome

AF:

0.0284

Gnomad EAS exome

AF:

0.00285

Gnomad FIN exome

AF:

0.0783

Gnomad NFE exome

AF:

0.0592

Gnomad OTH exome

AF:

0.0577

GnomAD4 exome

AF:

0.0606

AC:

88581

AN:

1460870

Hom.:

3553

Cov.:

AF XY:

0.0587

AC XY:

42660

AN XY:

726728

show subpopulations

African (AFR)

AF:

0.248

AC:

8298

AN:

33480

American (AMR)

AF:

0.0386

AC:

1727

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0258

AC:

674

AN:

26136

East Asian (EAS)

AF:

0.00194

AC:

AN:

39700

South Asian (SAS)

AF:

0.0270

AC:

2329

AN:

86256

European-Finnish (FIN)

AF:

0.0763

AC:

4003

AN:

52442

Middle Eastern (MID)

AF:

0.0519

AC:

299

AN:

5756

European-Non Finnish (NFE)

AF:

0.0605

AC:

67281

AN:

1112002

Other (OTH)

AF:

0.0645

AC:

3893

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

5901

11801

17702

23602

29503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2546

5092

7638

10184

12730

<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

AF:

0.108

AC:

16486

AN:

152090

Hom.:

1534

Cov.:

AF XY:

0.107

AC XY:

7927

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.248

AC:

10297

AN:

41492

American (AMR)

AF:

0.0565

AC:

864

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0277

AC:

AN:

3466

East Asian (EAS)

AF:

0.00484

AC:

AN:

5162

South Asian (SAS)

AF:

0.0246

AC:

118

AN:

4796

European-Finnish (FIN)

AF:

0.0748

AC:

793

AN:

10608

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0596

AC:

4047

AN:

67952

Other (OTH)

AF:

0.0986

AC:

208

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

689

1378

2066

2755

3444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0714

Hom.:

913

Bravo

AF:

0.114

Asia WGS

AF:

0.0580

AC:

203

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 15, 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. -

Smith-Magenis syndrome

Benign:1

May 05, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.035

(source)

DANN

Benign

0.33

PhyloP100

-3.1

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

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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