17-17793779-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAG

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.867_872delGCAGCA(p.Gln290_Gln291del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00343 in 1,353,310 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q289Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.020 ( 17 hom., cov: 0)

Exomes 𝑓: 0.0024 ( 0 hom. )

Consequence

RAI1
NM_030665.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

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-CCAGCAG-C is Benign according to our data. Variant chr17-17793779-CCAGCAG-C is described in ClinVar as Benign. ClinVar VariationId is 212015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.867_872delGCAGCA	p.Gln290_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.867_872delGCAGCA	p.Gln290_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1
RAI1	ENST00000395774.1 link	c.867_872delGCAGCA	p.Gln290_Gln291del	disruptive_inframe_deletion	Exon 2 of 2	2		ENSP00000379120.1		A8MXE8

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

1582

AN:

78808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00732

Gnomad ASJ

AF:

0.00508

Gnomad EAS

AF:

0.00933

Gnomad SAS

AF:

0.00245

Gnomad FIN

AF:

0.000165

Gnomad MID

AF:

0.00562

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.0123

GnomAD4 exome

AF:

0.00239

AC:

3041

AN:

1274412

Hom.:

AF XY:

0.00224

AC XY:

1413

AN XY:

630338

show subpopulations

African (AFR)

AF:

0.0425

AC:

1173

AN:

27598

American (AMR)

AF:

0.00373

AC:

118

AN:

31658

Ashkenazi Jewish (ASJ)

AF:

0.00265

AC:

AN:

23366

East Asian (EAS)

AF:

0.00156

AC:

AN:

18624

South Asian (SAS)

AF:

0.000502

AC:

AN:

55734

European-Finnish (FIN)

AF:

0.000698

AC:

AN:

45816

Middle Eastern (MID)

AF:

0.00495

AC:

AN:

4850

European-Non Finnish (NFE)

AF:

0.00132

AC:

1342

AN:

1015020

Other (OTH)

AF:

0.00450

AC:

233

AN:

51746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

130

260

391

521

651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

152

228

304

380

<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:

0.0203

AC:

1598

AN:

78898

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

756

AN XY:

37498

show subpopulations

African (AFR)

AF:

0.0606

AC:

1444

AN:

23818

American (AMR)

AF:

0.00732

AC:

AN:

5874

Ashkenazi Jewish (ASJ)

AF:

0.00508

AC:

AN:

1968

East Asian (EAS)

AF:

0.00936

AC:

AN:

748

South Asian (SAS)

AF:

0.00244

AC:

AN:

818

European-Finnish (FIN)

AF:

0.000165

AC:

AN:

6062

Middle Eastern (MID)

AF:

0.00602

AC:

AN:

166

European-Non Finnish (NFE)

AF:

0.00203

AC:

AN:

37986

Other (OTH)

AF:

0.0121

AC:

AN:

1078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

138

206

275

344

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:

0.00528

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 01, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 10, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Aug 19, 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

PhyloP100

4.9

Mutation Taster

=195/5

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