chr17-17793779-CCAGCAGCAGCAGCAG-C

Variant names:

• chr17-17793779-CCAGCAGCAGCAGCAG-C
• rs371983878
• NM_030665.4:c.858_872delGCAGCAGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_030665.4(RAI1):​c.858_872delGCAGCAGCAGCAGCA​(p.Gln287_Gln291del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000477 in 1,356,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: RAI1 NM_030665.4 disruptive_inframe_deletion
• Clinical Significance: 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-CCAGCAGCAGCAGCAG-C is Benign according to our data. Variant chr17-17793779-CCAGCAGCAGCAGCAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 588823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17793779-CCAGCAGCAGCAGCAG-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000697 (55/78922) while in subpopulation SAS AF= 0.00367 (3/818). AF 95% confidence interval is 0.000999. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4	c.858_872delGCAGCAGCAGCAGCA	p.Gln287_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.858_872delGCAGCAGCAGCAGCA	p.Gln287_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	1	NM_030665.4	ENSP00000323074.4
RAI1	ENST00000395774.1	c.858_872delGCAGCAGCAGCAGCA	p.Gln287_Gln291del	disruptive_inframe_deletion	Exon 2 of 2	2		ENSP00000379120.1

Frequencies

GnomAD3 genomes AF: 0.000698 AC: 55 AN: 78832 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000170

Gnomad ASJ AF: 0.000508

Gnomad EAS AF: 0.00133

Gnomad SAS AF: 0.00368

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000579

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000463 AC: 592 AN: 1277886 Hom.: 0 AF XY: 0.000464 AC XY: 293 AN XY: 632002

Gnomad4 AFR exome AF: 0.000454

Gnomad4 AMR exome AF: 0.0000631

Gnomad4 ASJ exome AF: 0.000688

Gnomad4 EAS exome AF: 0.000322

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.000325

Gnomad4 NFE exome AF: 0.000427

Gnomad4 OTH exome AF: 0.000520

GnomAD4 genome AF: 0.000697 AC: 55 AN: 78922 Hom.: 0 Cov.: 0 AF XY: 0.000560 AC XY: 21 AN XY: 37510

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.000170

Gnomad4 ASJ AF: 0.000508

Gnomad4 EAS AF: 0.00134

Gnomad4 SAS AF: 0.00367

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000579

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 24, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RAI1: BS1 -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Jul 26, 2021

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

Apr 02, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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;