NM_030665.4:c.5659+966T>C

Variant names:

• chr17-17804815-T-C
• rs11654081
• NM_030665.4:c.5659+966T>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.5659+966T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,060 control chromosomes in the GnomAD database, including 20,952 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 0.50 (20952 hom., cov: 32)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4	c.5659+966T>C		intron_variant	Intron 4 of 5	ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.5659+966T>C		intron_variant	Intron 4 of 5	1	NM_030665.4	ENSP00000323074.4

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76337 AN: 151942 Hom.: 20940 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.502 AC: 76389 AN: 152060 Hom.: 20952 Cov.: 32 AF XY: 0.492 AC XY: 36598 AN XY: 74336

African (AFR) AF: 0.356 AC: 14746 AN: 41462

American (AMR) AF: 0.443 AC: 6770 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1996 AN: 3472

East Asian (EAS) AF: 0.0906 AC: 470 AN: 5188

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4818

European-Finnish (FIN) AF: 0.589 AC: 6206 AN: 10540

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43214 AN: 67976

Other (OTH) AF: 0.509 AC: 1074 AN: 2112

Alfa AF: 0.547 Hom.: 6583

Bravo AF: 0.485

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.17
PhyloP100		-1.7
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: rs11654081; hg19: chr17-17708129; COSMIC: COSV55398242; COSMIC: COSV55398242;