17-17797478-C-T

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.4530C>T(p.Pro1510Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 1,613,206 control chromosomes in the GnomAD database, including 3,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 892 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2985 hom. )

Consequence

RAI1
NM_030665.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.392

Publications

10 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=-0.85).

BP6

Variant 17-17797478-C-T is Benign according to our data. Variant chr17-17797478-C-T is described in ClinVar as Benign. ClinVar VariationId is 96192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.392 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.4530C>T	p.Pro1510Pro	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.4530C>T	p.Pro1510Pro	synonymous_variant	Exon 3 of 6	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

13439

AN:

152096

Hom.:

886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.00482

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0741

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0588

Gnomad OTH

AF:

0.0789

GnomAD2 exomes

AF:

0.0553

AC:

13767

AN:

249068

AF XY:

0.0530

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.0322

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.00290

Gnomad FIN exome

AF:

0.0781

Gnomad NFE exome

AF:

0.0585

Gnomad OTH exome

AF:

0.0532

GnomAD4 exome

AF:

0.0584

AC:

85385

AN:

1460992

Hom.:

2985

Cov.:

AF XY:

0.0568

AC XY:

41269

AN XY:

726794

show subpopulations

African (AFR)

AF:

0.184

AC:

6138

AN:

33442

American (AMR)

AF:

0.0342

AC:

1525

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

672

AN:

26116

East Asian (EAS)

AF:

0.00194

AC:

AN:

39696

South Asian (SAS)

AF:

0.0268

AC:

2312

AN:

86236

European-Finnish (FIN)

AF:

0.0763

AC:

4042

AN:

52976

Middle Eastern (MID)

AF:

0.0468

AC:

270

AN:

5768

European-Non Finnish (NFE)

AF:

0.0600

AC:

66754

AN:

1111766

Other (OTH)

AF:

0.0596

AC:

3595

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

5508

11016

16524

22032

27540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2500

5000

7500

10000

12500

<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:

0.0886

AC:

13483

AN:

152214

Hom.:

892

Cov.:

AF XY:

0.0878

AC XY:

6532

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.182

AC:

7561

AN:

41518

American (AMR)

AF:

0.0454

AC:

694

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0277

AC:

AN:

3470

East Asian (EAS)

AF:

0.00484

AC:

AN:

5170

South Asian (SAS)

AF:

0.0238

AC:

115

AN:

4824

European-Finnish (FIN)

AF:

0.0741

AC:

787

AN:

10620

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0587

AC:

3994

AN:

67996

Other (OTH)

AF:

0.0833

AC:

176

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

596

1192

1788

2384

2980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0671

Hom.:

314

Bravo

AF:

0.0906

Asia WGS

AF:

0.0540

AC:

189

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

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

- -

PreventionGenetics, part of Exact Sciences

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

- -

Mar 03, 2015

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

- -

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 03, 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

-0.85

CADD

Benign

0.78

(source)

DANN

Benign

0.35

PhyloP100

0.39

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