Variant NM_030665.4:c.870_872delGCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_030665.4(RAI1):c.870_872delGCA(p.Gln291del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.083 in 1,213,010 control chromosomes in the GnomAD database, including 1,268 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 912 hom., cov: 0)

Exomes 𝑓: 0.077 ( 356 hom. )

Consequence

RAI1
NM_030665.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.55

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 -16 ACMG points.

BP6

Variant 17-17793779-CCAG-C is Benign according to our data. Variant chr17-17793779-CCAG-C is described in ClinVar as [Benign]. Clinvar id is 196559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17793779-CCAG-C is described in Lovd as [Likely_benign]. Variant chr17-17793779-CCAG-C is described in Lovd as [Benign]. Variant chr17-17793779-CCAG-C is described in Lovd as [Likely_benign]. Variant chr17-17793779-CCAG-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.870_872delGCA	p.Gln291del	disruptive_inframe_deletion	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.870_872delGCA	p.Gln291del	disruptive_inframe_deletion	Exon 3 of 6	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1
RAI1	ENST00000395774.1 link	c.870_872delGCA	p.Gln291del	disruptive_inframe_deletion	Exon 2 of 2	2		ENSP00000379120.1		A8MXE8

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

13457

AN:

78480

Hom.:

900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.0476

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.0428

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.121

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.144

GnomAD4 exome

AF:

0.0768

AC:

87122

AN:

1134446

Hom.:

356

AF XY:

0.0759

AC XY:

42355

AN XY:

558228

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.0647

Gnomad4 ASJ exome

AF:

0.0447

Gnomad4 EAS exome

AF:

0.00524

Gnomad4 SAS exome

AF:

0.0364

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.0741

Gnomad4 OTH exome

AF:

0.0839

GnomAD4 genome

AF:

0.172

AC:

13499

AN:

78564

Hom.:

912

Cov.:

AF XY:

0.174

AC XY:

6512

AN XY:

37326

show subpopulations

Gnomad4 AFR

AF:

0.321

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.0429

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.100

Gnomad4 OTH

AF:

0.152

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 03, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 30, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 27, 2014

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Sep 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Aug 26, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

RAI1-related disorder

Benign:1

Jul 19, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Smith-Magenis syndrome

Benign:1

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

African/African American population allele frequency is 30.36% (rs74986416, 1586/5010 alleles, 148 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.4.0, this variant is classified as BENIGN. Following criteria are met: BA1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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