17-17793779-CCAGCAG-C

Position:

• chr17-17793779-CCAGCAG-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.867_872del​(p.Gln290_Gln291del) variant causes a 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (17 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (0 hom.)
• Consequence: RAI1 NM_030665.4 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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-CCAGCAG-C is Benign according to our data. Variant chr17-17793779-CCAGCAG-C is described in ClinVar as [Benign]. Clinvar id is 212015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17793779-CCAGCAG-C is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
RAI1	NM_030665.4	c.867_872del	p.Gln290_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.867_872del	p.Gln290_Gln291del	inframe_deletion	3/6	1	NM_030665.4	ENSP00000323074	P1
RAI1	ENST00000395774.1	c.867_872del	p.Gln290_Gln291del	inframe_deletion	2/2	2		ENSP00000379120

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 1582 AN: 78808 Hom.: 17 Cov.: 0

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.: 0 AF XY: 0.00224 AC XY: 1413 AN XY: 630338

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.00373

Gnomad4 ASJ exome AF: 0.00265

Gnomad4 EAS exome AF: 0.00156

Gnomad4 SAS exome AF: 0.000502

Gnomad4 FIN exome AF: 0.000698

Gnomad4 NFE exome AF: 0.00132

Gnomad4 OTH exome AF: 0.00450

GnomAD4 genome AF: 0.0203 AC: 1598 AN: 78898 Hom.: 17 Cov.: 0 AF XY: 0.0202 AC XY: 756 AN XY: 37498

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.00508

Gnomad4 EAS AF: 0.00936

Gnomad4 SAS AF: 0.00244

Gnomad4 FIN AF: 0.000165

Gnomad4 NFE AF: 0.00203

Gnomad4 OTH AF: 0.0121

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 10, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 01, 2013	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 19, 2019	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2016

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

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;