17-17697265-T-G

Variant names:

• chr17-17697265-T-G
• rs7224617
• NM_030665.4:c.-149+15472T>G

Variant summary

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

The NM_030665.4(RAI1):​c.-149+15472T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,156 control chromosomes in the GnomAD database, including 23,306 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 0.53 (23306 hom., cov: 34)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• 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

ENSG00000294573 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 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.-149+15472T>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.-149+15472T>G		intron	N/A	ENSP00000323074.4
	RAI1	ENST00000471135.2	TSL:3	c.-149+13562T>G		intron	N/A	ENSP00000463607.1
	ENSG00000294573	ENST00000724466.1		n.106-1975T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80953 AN: 152038 Hom.: 23257 Cov.: 34

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.533 AC: 81056 AN: 152156 Hom.: 23306 Cov.: 34 AF XY: 0.517 AC XY: 38429 AN XY: 74388

African (AFR) AF: 0.733 AC: 30415 AN: 41510

American (AMR) AF: 0.399 AC: 6101 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1849 AN: 3472

East Asian (EAS) AF: 0.151 AC: 781 AN: 5180

South Asian (SAS) AF: 0.205 AC: 992 AN: 4828

European-Finnish (FIN) AF: 0.434 AC: 4582 AN: 10568

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34756 AN: 67984

Other (OTH) AF: 0.499 AC: 1056 AN: 2116

Alfa AF: 0.477 Hom.: 9135

Bravo AF: 0.541

Asia WGS AF: 0.246 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.61
PhyloP100		1.0
Mutation Taster		=99/1	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: rs7224617; hg19: chr17-17600579; COSMIC: COSV62167576;