chr17-17793401-G-A

Variant names:

• chr17-17793401-G-A
• rs767613627
• NM_030665.4:c.453G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_030665.4(RAI1):​c.453G>A​(p.Val151Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. V151V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: RAI1 NM_030665.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.227
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Smith-Magenis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Potocki-Lupski syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-17793401-G-A is Benign according to our data. Variant chr17-17793401-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2010371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.227 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000137 (20/1461408) while in subpopulation EAS AF = 0.000479 (19/39700). AF 95% confidence interval is 0.000313. There are 0 homozygotes in GnomAdExome4. There are 12 alleles in the male GnomAdExome4 subpopulation. Median coverage is 92. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030665.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI1	NM_030665.4	MANE Select	c.453G>A	p.Val151Val	synonymous	Exon 3 of 6	NP_109590.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI1	ENST00000353383.6	TSL:1 MANE Select	c.453G>A	p.Val151Val	synonymous	Exon 3 of 6	ENSP00000323074.4
	RAI1	ENST00000918590.1		c.453G>A	p.Val151Val	synonymous	Exon 2 of 5	ENSP00000588649.1
	RAI1	ENST00000955422.1		c.453G>A	p.Val151Val	synonymous	Exon 3 of 6	ENSP00000625481.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 250290 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461408 Hom.: 0 Cov.: 92 AF XY: 0.0000165 AC XY: 12 AN XY: 727008

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	RAI1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.5
DANN	Benign	0.42
PhyloP100		-0.23

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

Other links and lift over

dbSNP: rs767613627; hg19: chr17-17696715;