rs9914733

Variant names:

• chr17-17718822-C-G
• rs9914733
• NM_030665.4:c.-148-5206C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-17718822-C-G
• chr17-17718822-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030665.4(RAI1):​c.-148-5206C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,014 control chromosomes in the GnomAD database, including 4,985 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (4985 hom., cov: 31)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509
• Publications: 5 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: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Potocki-Lupski syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

LOC124903943 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI1	NM_030665.4	MANE Select	c.-148-5206C>G		intron	N/A	NP_109590.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI1	ENST00000353383.6	TSL:1 MANE Select	c.-148-5206C>G		intron	N/A	ENSP00000323074.4
	RAI1	ENST00000471135.2	TSL:3	c.-148-5206C>G		intron	N/A	ENSP00000463607.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38149 AN: 151896 Hom.: 4979 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.251 AC: 38184 AN: 152014 Hom.: 4985 Cov.: 31 AF XY: 0.251 AC XY: 18647 AN XY: 74306

African (AFR) AF: 0.293 AC: 12148 AN: 41446

American (AMR) AF: 0.265 AC: 4051 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1814 AN: 5166

South Asian (SAS) AF: 0.163 AC: 786 AN: 4822

European-Finnish (FIN) AF: 0.243 AC: 2564 AN: 10546

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15341 AN: 67972

Other (OTH) AF: 0.270 AC: 568 AN: 2106

Alfa AF: 0.227 Hom.: 520

Bravo AF: 0.261

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		-0.51
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

Other links and lift over

dbSNP: rs9914733; hg19: chr17-17622136; COSMIC: COSV62167623;