17-17793779-CCAGCAGCAG-C

Position:

• chr17-17793779-CCAGCAGCAG-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_030665.4(RAI1):​c.864_872del​(p.Gln289_Gln291del) variant causes a 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (15 hom., cov: 0)
  • Exomes 𝑓: 0.0051 (14 hom.)
• Consequence: RAI1 NM_030665.4 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 4.86

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-17793779-CCAGCAGCAG-C is Benign according to our data. Variant chr17-17793779-CCAGCAGCAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 196558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17793779-CCAGCAGCAG-C is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
RAI1	NM_030665.4	c.864_872del	p.Gln289_Gln291del	inframe_deletion	3/6	ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.864_872del	p.Gln289_Gln291del	inframe_deletion	3/6	1	NM_030665.4	ENSP00000323074	P1
RAI1	ENST00000395774.1	c.864_872del	p.Gln289_Gln291del	inframe_deletion	2/2	2		ENSP00000379120

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 954 AN: 78826 Hom.: 15 Cov.: 0

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.: 14 AF XY: 0.00510 AC XY: 3224 AN XY: 632452

Gnomad4 AFR exome AF: 0.00861

Gnomad4 AMR exome AF: 0.00429

Gnomad4 ASJ exome AF: 0.00385

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.00762

Gnomad4 FIN exome AF: 0.0140

Gnomad4 NFE exome AF: 0.00154

Gnomad4 OTH exome AF: 0.00818

GnomAD4 genome AF: 0.0121 AC: 954 AN: 78916 Hom.: 15 Cov.: 0 AF XY: 0.0140 AC XY: 524 AN XY: 37506

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.00813

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.00324

Gnomad4 OTH AF: 0.0176

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	RAI1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Oct 03, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 02, 2015

- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2018

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 04, 2019

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs371983878; hg19: chr17-17697093;