rs9914733

chr17-17718822-C-Gchr17-17718822-C-T

Variant summary

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

The NM_030665.4(RAI1):c.-148-5206C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,014 control chromosomes in the GnomAD database, including 4,985 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 0.25 (4985 hom., cov: 31)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

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]

LOC124903943 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAI1	NM_030665.4	c.-148-5206C>G		intron_variant		ENST00000353383.6
LOC124903943	XR_007065650.1	n.3499G>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAI1	ENST00000353383.6	c.-148-5206C>G		intron_variant		1	NM_030665.4	P1
RAI1	ENST00000471135.2	c.-148-5206C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38149 AN: 151896 Hom.: 4979 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.251 AC: 38184 AN: 152014 Hom.: 4985 Cov.: 31 AF XY: 0.251 AC XY: 18647 AN XY: 74306

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.270

Alfa AF: 0.227 Hom.: 520

Bravo AF: 0.261

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	10
Dann	Benign	0.75

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: rs9914733; hg19: chr17-17622136; COSMIC: COSV62167623;