17-17793779-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_030665.4(RAI1):c.864_872delGCAGCAGCA(p.Gln289_Gln291del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00546 in 1,357,646 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q288Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.012 ( 15 hom., cov: 0)

Exomes 𝑓: 0.0051 ( 14 hom. )

Consequence

RAI1
NM_030665.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.86

Publications

8 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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_030665.4

BP6

Variant 17-17793779-CCAGCAGCAG-C is Benign according to our data. Variant chr17-17793779-CCAGCAGCAG-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 196558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.864_872delGCAGCAGCA	p.Gln289_Gln291del	disruptive_inframe_deletion	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.864_872delGCAGCAGCA	p.Gln289_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1
RAI1	ENST00000395774.1 link	c.864_872delGCAGCAGCA	p.Gln289_Gln291del	disruptive_inframe_deletion	Exon 2 of 2	2		ENSP00000379120.1		A8MXE8

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

954

AN:

78826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.00813

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.0343

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0225

Gnomad NFE

AF:

0.00324

Gnomad OTH

AF:

0.0169

GnomAD4 exome

AF:

0.00506

AC:

6464

AN:

1278730

Hom.:

AF XY:

0.00510

AC XY:

3224

AN XY:

632452

show subpopulations

African (AFR)

AF:

0.00861

AC:

246

AN:

28572

American (AMR)

AF:

0.00429

AC:

136

AN:

31706

Ashkenazi Jewish (ASJ)

AF:

0.00385

AC:

AN:

23378

East Asian (EAS)

AF:

0.155

AC:

2889

AN:

18602

South Asian (SAS)

AF:

0.00762

AC:

425

AN:

55800

European-Finnish (FIN)

AF:

0.0140

AC:

646

AN:

46178

Middle Eastern (MID)

AF:

0.00802

AC:

AN:

4864

European-Non Finnish (NFE)

AF:

0.00154

AC:

1568

AN:

1017668

Other (OTH)

AF:

0.00818

AC:

425

AN:

51962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.407

Heterozygous variant carriers

420

840

1260

1680

2100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.0121

AC:

954

AN:

78916

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

524

AN XY:

37506

show subpopulations

African (AFR)

AF:

0.0102

AC:

244

AN:

23832

American (AMR)

AF:

0.0121

AC:

AN:

5874

Ashkenazi Jewish (ASJ)

AF:

0.00813

AC:

AN:

1968

East Asian (EAS)

AF:

0.422

AC:

315

AN:

746

South Asian (SAS)

AF:

0.0342

AC:

AN:

818

European-Finnish (FIN)

AF:

0.0221

AC:

134

AN:

6064

Middle Eastern (MID)

AF:

0.0241

AC:

AN:

166

European-Non Finnish (NFE)

AF:

0.00324

AC:

123

AN:

37988

Other (OTH)

AF:

0.0176

AC:

AN:

1080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Oct 03, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RAI1: BS1, BS2 -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 02, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jul 19, 2018

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely 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

Jul 04, 2019

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

PhyloP100

4.9

Mutation Taster

=198/2

polymorphism

(source)

Splicing

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