17-17697265-T-G

Position:

• chr17-17697265-T-G

Variant summary

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

The NM_030665.4(RAI1):​c.-149+15472T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,156 control chromosomes in the GnomAD database, including 23,306 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 0.53 (23306 hom., cov: 34)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI1	NM_030665.4	c.-149+15472T>G		intron_variant		ENST00000353383.6	NP_109590.3
RAI1	XM_047435151.1	c.-149+11077T>G		intron_variant			XP_047291107.1
RAI1	XM_047435152.1	c.-149+13562T>G		intron_variant			XP_047291108.1
RAI1	XM_047435153.1	c.-17+15472T>G		intron_variant			XP_047291109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.-149+15472T>G		intron_variant		1	NM_030665.4	ENSP00000323074	P1
RAI1	ENST00000471135.2	c.-149+13562T>G		intron_variant		3		ENSP00000463607

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80953 AN: 152038 Hom.: 23257 Cov.: 34

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.533 AC: 81056 AN: 152156 Hom.: 23306 Cov.: 34 AF XY: 0.517 AC XY: 38429 AN XY: 74388

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.499

Alfa AF: 0.468 Hom.: 7887

Bravo AF: 0.541

Asia WGS AF: 0.246 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.61

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: rs7224617; hg19: chr17-17600579; COSMIC: COSV62167576;