rs752579

Variant names:

• chr17-17757033-C-T
• rs752579
• NM_030665.4:c.-17+32874C>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.-17+32874C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,054 control chromosomes in the GnomAD database, including 17,019 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 0.42 (17019 hom., cov: 32)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 18 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4	c.-17+32874C>T		intron_variant	Intron 2 of 5	ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.-17+32874C>T		intron_variant	Intron 2 of 5	1	NM_030665.4	ENSP00000323074.4
RAI1	ENST00000471135.2	c.-17+32874C>T		intron_variant	Intron 3 of 3	3		ENSP00000463607.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 64039 AN: 151936 Hom.: 17019 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.421 AC: 64035 AN: 152054 Hom.: 17019 Cov.: 32 AF XY: 0.414 AC XY: 30744 AN XY: 74316

African (AFR) AF: 0.131 AC: 5451 AN: 41510

American (AMR) AF: 0.390 AC: 5963 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1930 AN: 3472

East Asian (EAS) AF: 0.125 AC: 645 AN: 5160

South Asian (SAS) AF: 0.205 AC: 991 AN: 4824

European-Finnish (FIN) AF: 0.593 AC: 6261 AN: 10560

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41187 AN: 67926

Other (OTH) AF: 0.434 AC: 917 AN: 2112

Alfa AF: 0.531 Hom.: 18130

Bravo AF: 0.397

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.58
PhyloP100		-0.96
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: rs752579; hg19: chr17-17660347;