17-17793785-G-A

Variant names:

• chr17-17793785-G-A
• rs11078398
• NM_030665.4:c.837G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_030665.4(RAI1):​c.837G>A​(p.Gln279Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (5 hom., cov: 0)
  • Exomes 𝑓: 0.0080 (32 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAI1 NM_030665.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.45
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-17793785-G-A is Benign according to our data. Variant chr17-17793785-G-A is described in ClinVar as Benign. ClinVar VariationId is 96198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 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.837G>A	p.Gln279Gln	synonymous	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.837G>A	p.Gln279Gln	synonymous	Exon 3 of 6	ENSP00000323074.4	Q7Z5J4-1
	RAI1	ENST00000918590.1		c.837G>A	p.Gln279Gln	synonymous	Exon 2 of 5	ENSP00000588649.1
	RAI1	ENST00000955422.1		c.837G>A	p.Gln279Gln	synonymous	Exon 3 of 6	ENSP00000625481.1

Frequencies

GnomAD3 genomes AF: 0.00530 AC: 287 AN: 54134 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00558

Gnomad ASJ AF: 0.00239

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.000254

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00353

Gnomad OTH AF: 0.00674

GnomAD2 exomes AF: 0.0489 AC: 9588 AN: 195896 AF XY: 0.0451

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.0367

Gnomad ASJ exome AF: 0.0208

Gnomad EAS exome AF: 0.0812

Gnomad FIN exome AF: 0.0864

Gnomad NFE exome AF: 0.0375

Gnomad OTH exome AF: 0.0390

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00796 AC: 4154 AN: 522176 Hom.: 32 Cov.: 0 AF XY: 0.00944 AC XY: 2402 AN XY: 254516

African (AFR) AF: 0.00315 AC: 20 AN: 6352

American (AMR) AF: 0.0123 AC: 84 AN: 6850

Ashkenazi Jewish (ASJ) AF: 0.00149 AC: 13 AN: 8720

East Asian (EAS) AF: 0.169 AC: 143 AN: 848

South Asian (SAS) AF: 0.163 AC: 1713 AN: 10490

European-Finnish (FIN) AF: 0.00882 AC: 146 AN: 16552

Middle Eastern (MID) AF: 0.0178 AC: 30 AN: 1682

European-Non Finnish (NFE) AF: 0.00389 AC: 1754 AN: 451456

Other (OTH) AF: 0.0131 AC: 251 AN: 19226

GnomAD4 genome AF: 0.00532 AC: 288 AN: 54172 Hom.: 5 Cov.: 0 AF XY: 0.00601 AC XY: 154 AN XY: 25640

African (AFR) AF: 0.00252 AC: 34 AN: 13488

American (AMR) AF: 0.00557 AC: 22 AN: 3948

Ashkenazi Jewish (ASJ) AF: 0.00239 AC: 3 AN: 1256

East Asian (EAS) AF: 0.315 AC: 34 AN: 108

South Asian (SAS) AF: 0.162 AC: 84 AN: 520

European-Finnish (FIN) AF: 0.000254 AC: 1 AN: 3936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 116

European-Non Finnish (NFE) AF: 0.00353 AC: 105 AN: 29734

Other (OTH) AF: 0.00665 AC: 5 AN: 752

Alfa AF: 0.259 Hom.: 2043

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	RAI1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11078398; hg19: chr17-17697099; COSMIC: COSV55388938; COSMIC: COSV55388938;