rs794727528

chr17-17793779-C-CCAGCAGCAGCAGCAGCAGchr17-17793779-CCAG-Cchr17-17793779-C-CCAGCAGCAGchr17-17793779-C-CCAGCAGCAGCAGCAGCAGCAGchr17-17793779-CCAGCAGCAGCAGCAGCAG-Cchr17-17793779-C-CCAGCAGCAGCAGCAGchr17-17793779-CCAGCAGCAGCAGCAGCAGCAG-Cchr17-17793779-C-CCAGCAGCAGCAGCAGCAGCAGCAGCAGchr17-17793779-C-CCAGCAGCAGCAGchr17-17793779-CCAGCAGCAGCAGCAG-Cchr17-17793779-C-CCAGCAGchr17-17793779-CCAGCAGCAGCAG-Cchr17-17793779-CCAGCAG-Cchr17-17793779-CCAGCAGCAGCAGCAGCAGCAGCAG-Cchr17-17793779-C-CCAGCAGCAGCAGCAGCAGCAGCAGchr17-17793779-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-Cchr17-17793779-C-CCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGchr17-17793779-CCAGCAGCAG-Cchr17-17793779-C-CCAG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_030665.4(RAI1):c.855_872dup(p.Gln286_Gln291dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000887 in 78,922 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000089 (1 hom., cov: 0)
  • Exomes 𝑓: 0.000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAI1 NM_030665.4 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.36

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 17-17793779-C-CCAGCAGCAGCAGCAGCAG is Benign according to our data. Variant chr17-17793779-C-CCAGCAGCAGCAGCAGCAG is described in ClinVar as [Likely_benign]. Clinvar id is 2044841.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAI1	NM_030665.4	c.855_872dup	p.Gln286_Gln291dup	inframe_insertion	3/6	ENST00000353383.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAI1	ENST00000353383.6	c.855_872dup	p.Gln286_Gln291dup	inframe_insertion	3/6	1	NM_030665.4	P1
RAI1	ENST00000395774.1	c.855_872dup	p.Gln286_Gln291dup	inframe_insertion	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0000888 AC: 7 AN: 78832 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0000421

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00123

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0225

Gnomad NFE AF: 0.0000263

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000172 AC: 22 AN: 1278808 Hom.: 0 Cov.: 38 AF XY: 0.0000206 AC XY: 13 AN XY: 632490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000537

Gnomad4 SAS exome AF: 0.0000358

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000983

Gnomad4 OTH exome AF: 0.0000192

GnomAD4 genome AF: 0.0000887 AC: 7 AN: 78922 Hom.: 1 Cov.: 0 AF XY: 0.000133 AC XY: 5 AN XY: 37510

Gnomad4 AFR AF: 0.0000420

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00122

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000263

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371983878; hg19: chr17-17697093;