chr17-17768172-G-C

Variant names:

• chr17-17768172-G-C
• rs11658846
• NM_030665.4:c.-16-24761G>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.-16-24761G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,226 control chromosomes in the GnomAD database, including 1,943 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 0.12 (1943 hom., cov: 33)
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 2 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-AS1 (HGNC:40496): (RAI1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4	c.-16-24761G>C		intron_variant	Intron 2 of 5	ENST00000353383.6	NP_109590.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6	c.-16-24761G>C		intron_variant	Intron 2 of 5	1	NM_030665.4	ENSP00000323074.4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18292 AN: 152108 Hom.: 1938 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0822

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0622

Gnomad OTH AF: 0.0971

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

GnomAD4 genome AF: 0.120 AC: 18314 AN: 152226 Hom.: 1943 Cov.: 33 AF XY: 0.117 AC XY: 8718 AN XY: 74436

African (AFR) AF: 0.286 AC: 11879 AN: 41502

American (AMR) AF: 0.0569 AC: 870 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 96 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5188

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4828

European-Finnish (FIN) AF: 0.0822 AC: 871 AN: 10600

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0622 AC: 4230 AN: 68024

Other (OTH) AF: 0.103 AC: 217 AN: 2112

Alfa AF: 0.0286 Hom.: 15

Bravo AF: 0.126

Asia WGS AF: 0.0570 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.74
PhyloP100		-0.79
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: rs11658846; hg19: chr17-17671486;