chr17-17794940-G-A

Variant names:

Variant summary

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

The NM_030665.4(RAI1):c.1992G>A(p.Pro664Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,613,474 control chromosomes in the GnomAD database, including 291,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25281 hom., cov: 34)

Exomes 𝑓: 0.59 ( 265761 hom. )

Consequence

RAI1
NM_030665.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -3.42

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=-0.84).

BP6

Variant 17-17794940-G-A is Benign according to our data. Variant chr17-17794940-G-A is described in ClinVar as [Benign]. Clinvar id is 96179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17794940-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.1992G>A	p.Pro664Pro	synonymous_variant	Exon 3 of 6	ENST00000353383.6	NP_109590.3	Q7Z5J4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6 link	c.1992G>A	p.Pro664Pro	synonymous_variant	Exon 3 of 6	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1
RAI1	ENST00000395774.1 link	c.1992G>A	p.Pro664Pro	synonymous_variant	Exon 2 of 2	2		ENSP00000379120.1		A8MXE8

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85946

AN:

152060

Hom.:

25254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.577

Gnomad AMI

AF:

0.548

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.564

GnomAD3 exomes

AF:

0.502

AC:

125894

AN:

250822

Hom.:

35084

AF XY:

0.498

AC XY:

67531

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.569

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.596

Gnomad NFE exome

AF:

0.628

Gnomad OTH exome

AF:

0.537

GnomAD4 exome

AF:

0.590

AC:

861867

AN:

1461296

Hom.:

265761

Cov.:

108

AF XY:

0.580

AC XY:

421992

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.561

Gnomad4 AMR exome

AF:

0.387

Gnomad4 ASJ exome

AF:

0.556

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.598

Gnomad4 NFE exome

AF:

0.641

Gnomad4 OTH exome

AF:

0.566

GnomAD4 genome

AF:

0.565

AC:

86029

AN:

152178

Hom.:

25281

Cov.:

AF XY:

0.554

AC XY:

41192

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.577

Gnomad4 AMR

AF:

0.471

Gnomad4 ASJ

AF:

0.562

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.581

Gnomad4 NFE

AF:

0.631

Gnomad4 OTH

AF:

0.566

Alfa

AF:

0.608

Hom.:

37521

Bravo

AF:

0.559

Asia WGS

AF:

0.282

AC:

984

AN:

3478

EpiCase

AF:

0.618

EpiControl

AF:

0.611

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 04, 2025	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Smith-Magenis syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 05, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0050

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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