rs11654081

Positions:

• chr17-17804815-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030665.4(RAI1):​c.5659+966T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,060 control chromosomes in the GnomAD database, including 20,952 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 0.50 (20952 hom., cov: 32)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI1	NM_030665.4	c.5659+966T>C		intron_variant		ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.5659+966T>C		intron_variant		1	NM_030665.4	ENSP00000323074.4

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76337 AN: 151942 Hom.: 20940 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.502 AC: 76389 AN: 152060 Hom.: 20952 Cov.: 32 AF XY: 0.492 AC XY: 36598 AN XY: 74336

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.509

Alfa AF: 0.557 Hom.: 5719

Bravo AF: 0.485

Asia WGS AF: 0.238 AC: 828 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	0.26
DANN	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs11654081; hg19: chr17-17708129; COSMIC: COSV55398242; COSMIC: COSV55398242;