dbSNP rs4925114: RAI1:c.5660-1434A>G (chr17-17807956-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030665.4(RAI1):c.5660-1434A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,060 control chromosomes in the GnomAD database, including 22,460 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 0.53 ( 22460 hom., cov: 33)

Consequence

RAI1
NM_030665.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI1	NM_030665.4 link	c.5660-1434A>G		intron_variant	Intron 4 of 5	ENST00000353383.6	NP_109590.3	Q7Z5J4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI1	ENST00000353383.6 link	c.5660-1434A>G		intron_variant	Intron 4 of 5	1	NM_030665.4	ENSP00000323074.4		Q7Z5J4-1

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79837

AN:

151940

Hom.:

22444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.575

Gnomad EAS

AF:

0.0964

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.638

Gnomad OTH

AF:

0.519

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

GnomAD4 genome

AF:

0.525

AC:

79900

AN:

152060

Hom.:

22460

Cov.:

AF XY:

0.517

AC XY:

38458

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.454

Gnomad4 ASJ

AF:

0.575

Gnomad4 EAS

AF:

0.0962

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.633

Gnomad4 NFE

AF:

0.638

Gnomad4 OTH

AF:

0.522

Alfa

AF:

0.573

Hom.:

10787

Bravo

AF:

0.508

Asia WGS

AF:

0.245

AC:

853

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.29

DANN

Benign

0.66

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over