NM_030665.4:c.864_872delGCAGCAGCA

Variant names:

• chr17-17793779-CCAGCAGCAG-C
• rs371983878
• NM_030665.4:c.864_872delGCAGCAGCA

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_030665.4(RAI1):​c.864_872delGCAGCAGCA​(p.Gln289_Gln291del) variant causes a disruptive 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Q288Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.012 (15 hom., cov: 0)
  • Exomes 𝑓: 0.0051 (14 hom.)
• Consequence: RAI1 NM_030665.4 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• 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-CCAGCAGCAG-C is Benign according to our data. Variant chr17-17793779-CCAGCAGCAG-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 196558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

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.864_872delGCAGCAGCA	p.Gln289_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.864_872delGCAGCAGCA	p.Gln289_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	ENSP00000323074.4	Q7Z5J4-1
	RAI1	ENST00000918590.1		c.864_872delGCAGCAGCA	p.Gln289_Gln291del	disruptive_inframe_deletion	Exon 2 of 5	ENSP00000588649.1
	RAI1	ENST00000955422.1		c.864_872delGCAGCAGCA	p.Gln289_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	ENSP00000625481.1

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

African (AFR) AF: 0.00861 AC: 246 AN: 28572

American (AMR) AF: 0.00429 AC: 136 AN: 31706

Ashkenazi Jewish (ASJ) AF: 0.00385 AC: 90 AN: 23378

East Asian (EAS) AF: 0.155 AC: 2889 AN: 18602

South Asian (SAS) AF: 0.00762 AC: 425 AN: 55800

European-Finnish (FIN) AF: 0.0140 AC: 646 AN: 46178

Middle Eastern (MID) AF: 0.00802 AC: 39 AN: 4864

European-Non Finnish (NFE) AF: 0.00154 AC: 1568 AN: 1017668

Other (OTH) AF: 0.00818 AC: 425 AN: 51962

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

African (AFR) AF: 0.0102 AC: 244 AN: 23832

American (AMR) AF: 0.0121 AC: 71 AN: 5874

Ashkenazi Jewish (ASJ) AF: 0.00813 AC: 16 AN: 1968

East Asian (EAS) AF: 0.422 AC: 315 AN: 746

South Asian (SAS) AF: 0.0342 AC: 28 AN: 818

European-Finnish (FIN) AF: 0.0221 AC: 134 AN: 6064

Middle Eastern (MID) AF: 0.0241 AC: 4 AN: 166

European-Non Finnish (NFE) AF: 0.00324 AC: 123 AN: 37988

Other (OTH) AF: 0.0176 AC: 19 AN: 1080

Alfa AF: 0.00 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	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		=198/2	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; COSMIC: COSV99884402; COSMIC: COSV99884402;