Variant 17-17793779-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_030665.4(RAI1):c.870_872dup(p.Gln290dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 1,356,272 control chromosomes in the GnomAD database, including 42 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 26 hom., cov: 0)

Exomes 𝑓: 0.020 ( 16 hom. )

Consequence

RAI1
NM_030665.4 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.36

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 17-17793779-C-CCAG is Benign according to our data. Variant chr17-17793779-C-CCAG is described in ClinVar as [Benign]. Clinvar id is 130086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI1	NM_030665.4 linkuse as main transcript	c.870_872dup	p.Gln290dup	inframe_insertion	3/6	ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6 linkuse as main transcript	c.870_872dup	p.Gln290dup	inframe_insertion	3/6	1	NM_030665.4	ENSP00000323074	P1	Q7Z5J4-1
RAI1	ENST00000395774.1 linkuse as main transcript	c.870_872dup	p.Gln290dup	inframe_insertion	2/2	2		ENSP00000379120

Frequencies

GnomAD3 genomes

AF:

0.0330

AC:

2599

AN:

78794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.00533

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.0307

Gnomad MID

AF:

0.0281

Gnomad NFE

AF:

0.0374

Gnomad OTH

AF:

0.0282

GnomAD4 exome

AF:

0.0205

AC:

26172

AN:

1277388

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

13483

AN XY:

631784

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.0184

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.00177

Gnomad4 SAS exome

AF:

0.0408

Gnomad4 FIN exome

AF:

0.0188

Gnomad4 NFE exome

AF:

0.0202

Gnomad4 OTH exome

AF:

0.0184

GnomAD4 genome

AF:

0.0329

AC:

2598

AN:

78884

Hom.:

Cov.:

AF XY:

0.0344

AC XY:

1289

AN XY:

37498

show subpopulations

Gnomad4 AFR

AF:

0.0240

Gnomad4 AMR

AF:

0.0351

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.00535

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.0307

Gnomad4 NFE

AF:

0.0373

Gnomad4 OTH

AF:

0.0287

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 06, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 30, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Oct 16, 2015	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 08, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	RAI1: BS1, BS2 -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2018

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over