chr17-17793779-CCAGCAG-C

Variant names:

• chr17-17793779-CCAGCAG-C
• rs371983878
• NM_030665.4:c.867_872delGCAGCA

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.867_872delGCAGCA​(p.Gln290_Gln291del) variant causes a disruptive 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Q289Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.020 (17 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (0 hom.)
• Consequence: RAI1 NM_030665.4 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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-CCAGCAG-C is Benign according to our data. Variant chr17-17793779-CCAGCAG-C is described in ClinVar as Benign. ClinVar VariationId is 212015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 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.867_872delGCAGCA	p.Gln290_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.867_872delGCAGCA	p.Gln290_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	ENSP00000323074.4	Q7Z5J4-1
	RAI1	ENST00000918590.1		c.867_872delGCAGCA	p.Gln290_Gln291del	disruptive_inframe_deletion	Exon 2 of 5	ENSP00000588649.1
	RAI1	ENST00000955422.1		c.867_872delGCAGCA	p.Gln290_Gln291del	disruptive_inframe_deletion	Exon 3 of 6	ENSP00000625481.1

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

African (AFR) AF: 0.0425 AC: 1173 AN: 27598

American (AMR) AF: 0.00373 AC: 118 AN: 31658

Ashkenazi Jewish (ASJ) AF: 0.00265 AC: 62 AN: 23366

East Asian (EAS) AF: 0.00156 AC: 29 AN: 18624

South Asian (SAS) AF: 0.000502 AC: 28 AN: 55734

European-Finnish (FIN) AF: 0.000698 AC: 32 AN: 45816

Middle Eastern (MID) AF: 0.00495 AC: 24 AN: 4850

European-Non Finnish (NFE) AF: 0.00132 AC: 1342 AN: 1015020

Other (OTH) AF: 0.00450 AC: 233 AN: 51746

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

African (AFR) AF: 0.0606 AC: 1444 AN: 23818

American (AMR) AF: 0.00732 AC: 43 AN: 5874

Ashkenazi Jewish (ASJ) AF: 0.00508 AC: 10 AN: 1968

East Asian (EAS) AF: 0.00936 AC: 7 AN: 748

South Asian (SAS) AF: 0.00244 AC: 2 AN: 818

European-Finnish (FIN) AF: 0.000165 AC: 1 AN: 6062

Middle Eastern (MID) AF: 0.00602 AC: 1 AN: 166

European-Non Finnish (NFE) AF: 0.00203 AC: 77 AN: 37986

Other (OTH) AF: 0.0121 AC: 13 AN: 1078

Alfa AF: 0.00528 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9
Mutation Taster		=195/5	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: COSV55388700; COSMIC: COSV55388700;