NM_030665.4:c.837G>A

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.837G>A(p.Gln279Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 0)

Exomes 𝑓: 0.0080 ( 32 hom. )

Failed GnomAD Quality Control

Consequence

RAI1
NM_030665.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.45

Publications

16 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=-0.65).

BP6

Variant 17-17793785-G-A is Benign according to our data. Variant chr17-17793785-G-A is described in ClinVar as Benign. ClinVar VariationId is 96198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.837G>A	p.Gln279Gln	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.837G>A	p.Gln279Gln	synonymous_variant	Exon 3 of 6	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1
RAI1	ENST00000395774.1 link	c.837G>A	p.Gln279Gln	synonymous_variant	Exon 2 of 2	2		ENSP00000379120.1		A8MXE8

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

287

AN:

54134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00558

Gnomad ASJ

AF:

0.00239

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.000254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00353

Gnomad OTH

AF:

0.00674

GnomAD2 exomes

AF:

0.0489

AC:

9588

AN:

195896

AF XY:

0.0451

show subpopulations

Gnomad AFR exome

AF:

0.0541

Gnomad AMR exome

AF:

0.0367

Gnomad ASJ exome

AF:

0.0208

Gnomad EAS exome

AF:

0.0812

Gnomad FIN exome

AF:

0.0864

Gnomad NFE exome

AF:

0.0375

Gnomad OTH exome

AF:

0.0390

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00796

AC:

4154

AN:

522176

Hom.:

Cov.:

AF XY:

0.00944

AC XY:

2402

AN XY:

254516

show subpopulations

African (AFR)

AF:

0.00315

AC:

AN:

6352

American (AMR)

AF:

0.0123

AC:

AN:

6850

Ashkenazi Jewish (ASJ)

AF:

0.00149

AC:

AN:

8720

East Asian (EAS)

AF:

0.169

AC:

143

AN:

848

South Asian (SAS)

AF:

0.163

AC:

1713

AN:

10490

European-Finnish (FIN)

AF:

0.00882

AC:

146

AN:

16552

Middle Eastern (MID)

AF:

0.0178

AC:

AN:

1682

European-Non Finnish (NFE)

AF:

0.00389

AC:

1754

AN:

451456

Other (OTH)

AF:

0.0131

AC:

251

AN:

19226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

231

462

692

923

1154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.00532

AC:

288

AN:

54172

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

154

AN XY:

25640

show subpopulations

African (AFR)

AF:

0.00252

AC:

AN:

13488

American (AMR)

AF:

0.00557

AC:

AN:

3948

Ashkenazi Jewish (ASJ)

AF:

0.00239

AC:

AN:

1256

East Asian (EAS)

AF:

0.315

AC:

AN:

108

South Asian (SAS)

AF:

0.162

AC:

AN:

520

European-Finnish (FIN)

AF:

0.000254

AC:

AN:

3936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

116

European-Non Finnish (NFE)

AF:

0.00353

AC:

105

AN:

29734

Other (OTH)

AF:

0.00665

AC:

AN:

752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.259

Hom.:

2043

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Mar 18, 2014

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 15, 2013

Eurofins Ntd Llc (ga)

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:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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. -

RAI1-related disorder

Benign:1

Jun 20, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.90

(source)

DANN

Benign

0.39

PhyloP100

2.5

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