chr17-17724827-T-C

Variant names:

• chr17-17724827-T-C
• rs9907986
• NM_030665.4:c.-17+668T>C

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+668T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 151,934 control chromosomes in the GnomAD database, including 34,556 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 0.67 (34556 hom., cov: 31)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4	c.-17+668T>C		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+668T>C		intron_variant	Intron 2 of 5	1	NM_030665.4	ENSP00000323074.4
RAI1	ENST00000471135.2	c.-17+668T>C		intron_variant	Intron 3 of 3	3		ENSP00000463607.1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 100927 AN: 151816 Hom.: 34499 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.665 AC: 101044 AN: 151934 Hom.: 34556 Cov.: 31 AF XY: 0.651 AC XY: 48357 AN XY: 74232

African (AFR) AF: 0.791 AC: 32796 AN: 41482

American (AMR) AF: 0.601 AC: 9186 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2385 AN: 3466

East Asian (EAS) AF: 0.465 AC: 2384 AN: 5132

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4814

European-Finnish (FIN) AF: 0.587 AC: 6185 AN: 10536

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44615 AN: 67898

Other (OTH) AF: 0.664 AC: 1402 AN: 2112

Alfa AF: 0.661 Hom.: 4914

Bravo AF: 0.682

Asia WGS AF: 0.446 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	18
DANN	Benign	0.71
PhyloP100		0.082
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9907986; hg19: chr17-17628141;