17-17751005-A-G

Variant names:

• chr17-17751005-A-G
• rs11656775
• NM_030665.4:c.-17+26846A>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.-17+26846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,124 control chromosomes in the GnomAD database, including 28,716 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 0.60 (28716 hom., cov: 33)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 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.-17+26846A>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.-17+26846A>G		intron	N/A	ENSP00000323074.4
	RAI1	ENST00000471135.2	TSL:3	c.-17+26846A>G		intron	N/A	ENSP00000463607.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91626 AN: 152006 Hom.: 28679 Cov.: 33

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.603 AC: 91714 AN: 152124 Hom.: 28716 Cov.: 33 AF XY: 0.590 AC XY: 43868 AN XY: 74382

African (AFR) AF: 0.625 AC: 25918 AN: 41478

American (AMR) AF: 0.483 AC: 7382 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2127 AN: 3472

East Asian (EAS) AF: 0.153 AC: 790 AN: 5178

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4824

European-Finnish (FIN) AF: 0.630 AC: 6663 AN: 10574

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45641 AN: 67988

Other (OTH) AF: 0.587 AC: 1240 AN: 2112

Alfa AF: 0.561 Hom.: 1914

Bravo AF: 0.595

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.69
PhyloP100		-0.082
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: rs11656775; hg19: chr17-17654319; COSMIC: COSV62167697;