rs398124421

Positions:

• chr17-17793788-G-A
• chr17-17793788-G-C
• chr17-17793788-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_030665.4(RAI1):​c.840G>A​(p.Gln280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: RAI1 NM_030665.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.466

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-17793788-G-A is Benign according to our data. Variant chr17-17793788-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 96199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-17793788-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.466 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI1	NM_030665.4	c.840G>A	p.Gln280=	synonymous_variant	3/6	ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.840G>A	p.Gln280=	synonymous_variant	3/6	1	NM_030665.4	ENSP00000323074	P1
RAI1	ENST00000395774.1	c.840G>A	p.Gln280=	synonymous_variant	2/2	2		ENSP00000379120

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00123 AC: 227 AN: 184186 Hom.: 13 AF XY: 0.00108 AC XY: 110 AN XY: 101796

Gnomad AFR exome AF: 0.00131

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.000263

Gnomad EAS exome AF: 0.00535

Gnomad SAS exome AF: 0.00224

Gnomad FIN exome AF: 0.000896

Gnomad NFE exome AF: 0.000382

Gnomad OTH exome AF: 0.00159

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.274 Hom.: 70

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 01, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 10, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 06, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.9
DANN	Benign	0.64

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: rs398124421; hg19: chr17-17697102; COSMIC: COSV55391242; COSMIC: COSV55391242;