rs4925114

Variant names:

• chr17-17807956-A-G
• rs4925114
• NM_030665.4:c.5660-1434A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-17807956-A-G
• chr17-17807956-A-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.5660-1434A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,060 control chromosomes in the GnomAD database, including 22,460 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 (22460 hom., cov: 33)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 29 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 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.5660-1434A>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.5660-1434A>G		intron	N/A	ENSP00000323074.4

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79837 AN: 151940 Hom.: 22444 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.0964

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.525 AC: 79900 AN: 152060 Hom.: 22460 Cov.: 33 AF XY: 0.517 AC XY: 38458 AN XY: 74346

African (AFR) AF: 0.420 AC: 17397 AN: 41442

American (AMR) AF: 0.454 AC: 6930 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3470

East Asian (EAS) AF: 0.0962 AC: 497 AN: 5168

South Asian (SAS) AF: 0.255 AC: 1232 AN: 4826

European-Finnish (FIN) AF: 0.633 AC: 6699 AN: 10590

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43364 AN: 67968

Other (OTH) AF: 0.522 AC: 1102 AN: 2112

Alfa AF: 0.579 Hom.: 12334

Bravo AF: 0.508

Asia WGS AF: 0.245 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.66
PhyloP100		-1.3
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: rs4925114; hg19: chr17-17711270; COSMIC: COSV55400295; COSMIC: COSV55400295;