17-17693437-G-C

Variant names:

• chr17-17693437-G-C
• rs4925102
• NM_030665.4:c.-149+11644G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030665.4(RAI1):​c.-149+11644G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,132 control chromosomes in the GnomAD database, including 21,412 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (21412 hom., cov: 33)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 8 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

ENSG00000294573 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4	c.-149+11644G>C		intron_variant	Intron 1 of 5	ENST00000353383.6	NP_109590.3
RAI1	XM_047435151.1	c.-149+7249G>C		intron_variant	Intron 3 of 7		XP_047291107.1
RAI1	XM_047435152.1	c.-149+9734G>C		intron_variant	Intron 2 of 6		XP_047291108.1
RAI1	XM_047435153.1	c.-17+11644G>C		intron_variant	Intron 1 of 4		XP_047291109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.-149+11644G>C		intron_variant	Intron 1 of 5	1	NM_030665.4	ENSP00000323074.4
RAI1	ENST00000471135.2	c.-149+9734G>C		intron_variant	Intron 2 of 3	3		ENSP00000463607.1
ENSG00000294573	ENST00000724466.1	n.106-5803G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78167 AN: 152014 Hom.: 21364 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.514 AC: 78268 AN: 152132 Hom.: 21412 Cov.: 33 AF XY: 0.499 AC XY: 37124 AN XY: 74352

African (AFR) AF: 0.671 AC: 27849 AN: 41532

American (AMR) AF: 0.393 AC: 6004 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1827 AN: 3468

East Asian (EAS) AF: 0.144 AC: 746 AN: 5176

South Asian (SAS) AF: 0.205 AC: 989 AN: 4816

European-Finnish (FIN) AF: 0.434 AC: 4595 AN: 10582

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34711 AN: 67964

Other (OTH) AF: 0.486 AC: 1026 AN: 2112

Alfa AF: 0.512 Hom.: 2532

Bravo AF: 0.521

Asia WGS AF: 0.241 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs4925102; hg19: chr17-17596751; COSMIC: COSV62167569;