17-17768172-G-C

Position:

• chr17-17768172-G-C

Variant summary

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

The NM_030665.4(RAI1):​c.-16-24761G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,226 control chromosomes in the GnomAD database, including 1,943 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 0.12 (1943 hom., cov: 33)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI1	NM_030665.4	c.-16-24761G>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.-16-24761G>C		intron_variant		1	NM_030665.4	ENSP00000323074.4
RAI1	ENST00000471135.2	c.-16-24761G>C		intron_variant		3		ENSP00000463607.1
RAI1-AS1	ENST00000443696.1	n.7-1870C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18292 AN: 152108 Hom.: 1938 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0822

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0622

Gnomad OTH AF: 0.0971

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

GnomAD4 genome AF: 0.120 AC: 18314 AN: 152226 Hom.: 1943 Cov.: 33 AF XY: 0.117 AC XY: 8718 AN XY: 74436

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.0822

Gnomad4 NFE AF: 0.0622

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0286 Hom.: 15

Bravo AF: 0.126

Asia WGS AF: 0.0570 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.74

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: rs11658846; hg19: chr17-17671486;