Variant chr17-17797478-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030665.4(RAI1):c.4530C>T(p.Pro1510Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 1,613,206 control chromosomes in the GnomAD database, including 3,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 892 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2985 hom. )

Consequence

RAI1
NM_030665.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.392

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-17797478-C-T is Benign according to our data. Variant chr17-17797478-C-T is described in ClinVar as [Benign]. Clinvar id is 96192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17797478-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.392 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.4530C>T	p.Pro1510Pro	synonymous_variant	3/6	ENST00000353383.6	NP_109590.3	Q7Z5J4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6 link	c.4530C>T	p.Pro1510Pro	synonymous_variant	3/6	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

13439

AN:

152096

Hom.:

886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.00482

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0741

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0588

Gnomad OTH

AF:

0.0789

GnomAD3 exomes

AF:

0.0553

AC:

13767

AN:

249068

Hom.:

640

AF XY:

0.0530

AC XY:

7168

AN XY:

135294

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.0322

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.00290

Gnomad SAS exome

AF:

0.0269

Gnomad FIN exome

AF:

0.0781

Gnomad NFE exome

AF:

0.0585

Gnomad OTH exome

AF:

0.0532

GnomAD4 exome

AF:

0.0584

AC:

85385

AN:

1460992

Hom.:

2985

Cov.:

AF XY:

0.0568

AC XY:

41269

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.0342

Gnomad4 ASJ exome

AF:

0.0257

Gnomad4 EAS exome

AF:

0.00194

Gnomad4 SAS exome

AF:

0.0268

Gnomad4 FIN exome

AF:

0.0763

Gnomad4 NFE exome

AF:

0.0600

Gnomad4 OTH exome

AF:

0.0596

GnomAD4 genome

AF:

0.0886

AC:

13483

AN:

152214

Hom.:

892

Cov.:

AF XY:

0.0878

AC XY:

6532

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.0454

Gnomad4 ASJ

AF:

0.0277

Gnomad4 EAS

AF:

0.00484

Gnomad4 SAS

AF:

0.0238

Gnomad4 FIN

AF:

0.0741

Gnomad4 NFE

AF:

0.0587

Gnomad4 OTH

AF:

0.0833

Alfa

AF:

0.0697

Hom.:

255

Bravo

AF:

0.0906

Asia WGS

AF:

0.0540

AC:

189

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 22, 2014	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Smith-Magenis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.78

DANN

Benign

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over