17-17791447-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030665.4(RAI1):c.-16-1486G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 150,416 control chromosomes in the GnomAD database, including 384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.061 (384 hom., cov: 32)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0600

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-17791447-G-A is Benign according to our data. Variant chr17-17791447-G-A is described in ClinVar as [Benign]. Clinvar id is 1261147.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAI1	NM_030665.4	c.-16-1486G>A		intron_variant		ENST00000353383.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAI1	ENST00000353383.6	c.-16-1486G>A		intron_variant		1	NM_030665.4	P1
RAI1	ENST00000395774.1	c.-16-1486G>A		intron_variant		2
RAI1	ENST00000471135.2	c.-16-1486G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9122 AN: 150302 Hom.: 382 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0210

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0243

Gnomad EAS AF: 0.00374

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0568

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

GnomAD4 genome AF: 0.0607 AC: 9136 AN: 150416 Hom.: 384 Cov.: 32 AF XY: 0.0575 AC XY: 4210 AN XY: 73246

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0243

Gnomad4 EAS AF: 0.00375

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0349

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0241 Hom.: 12

Bravo AF: 0.0619

Asia WGS AF: 0.0470 AC: 167 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.4
Dann	Benign	0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99

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: rs11656699; hg19: chr17-17694761; COSMIC: COSV55398209; COSMIC: COSV55398209;