17-17793779-CCAGCAGCAGCAGCAG-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 8 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
• Potocki-Lupski syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_030665.4
• 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 VariationId is 588823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 55 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030665.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI1	NM_030665.4	MANE Select	c.858_872delGCAGCAGCAGCAGCA	p.Gln287_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	NP_109590.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI1	ENST00000353383.6	TSL:1 MANE Select	c.858_872delGCAGCAGCAGCAGCA	p.Gln287_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	ENSP00000323074.4	Q7Z5J4-1
	RAI1	ENST00000918590.1		c.858_872delGCAGCAGCAGCAGCA	p.Gln287_Gln291del	disruptive_inframe_deletion	Exon 2 of 5	ENSP00000588649.1
	RAI1	ENST00000955422.1		c.858_872delGCAGCAGCAGCAGCA	p.Gln287_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	ENSP00000625481.1

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

African (AFR) AF: 0.000454 AC: 13 AN: 28606

American (AMR) AF: 0.0000631 AC: 2 AN: 31686

Ashkenazi Jewish (ASJ) AF: 0.000688 AC: 16 AN: 23268

East Asian (EAS) AF: 0.000322 AC: 6 AN: 18624

South Asian (SAS) AF: 0.00109 AC: 61 AN: 55802

European-Finnish (FIN) AF: 0.000325 AC: 15 AN: 46138

Middle Eastern (MID) AF: 0.00370 AC: 18 AN: 4864

European-Non Finnish (NFE) AF: 0.000427 AC: 434 AN: 1016976

Other (OTH) AF: 0.000520 AC: 27 AN: 51922

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

African (AFR) AF: 0.00113 AC: 27 AN: 23834

American (AMR) AF: 0.000170 AC: 1 AN: 5874

Ashkenazi Jewish (ASJ) AF: 0.000508 AC: 1 AN: 1968

East Asian (EAS) AF: 0.00134 AC: 1 AN: 748

South Asian (SAS) AF: 0.00367 AC: 3 AN: 818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.000579 AC: 22 AN: 37988

Other (OTH) AF: 0.00 AC: 0 AN: 1080

Alfa AF: 0.00126 Hom.: 2

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	1	Inborn genetic diseases (1)
-	-	1	RAI1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9
Mutation Taster		=149/51	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs371983878; hg19: chr17-17697093;