17-17724233-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_030665.4(RAI1):c.-17+74G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 150,892 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAI1 NM_030665.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.533

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-17724233-G-T is Benign according to our data. Variant chr17-17724233-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1342813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00278 (419/150892) while in subpopulation AFR AF= 0.0098 (404/41210). AF 95% confidence interval is 0.00901. There are 2 homozygotes in gnomad4. There are 200 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd at 419 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAI1	NM_030665.4	c.-17+74G>T		intron_variant		ENST00000353383.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAI1	ENST00000353383.6	c.-17+74G>T		intron_variant		1	NM_030665.4	P1
RAI1	ENST00000471135.2	c.-17+74G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00278 AC: 419 AN: 150784 Hom.: 2 Cov.: 28

Gnomad AFR AF: 0.00981

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000527

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000444

Gnomad OTH AF: 0.00193

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 140 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 86

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00278 AC: 419 AN: 150892 Hom.: 2 Cov.: 28 AF XY: 0.00271 AC XY: 200 AN XY: 73686

Gnomad4 AFR AF: 0.00980

Gnomad4 AMR AF: 0.000527

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000444

Gnomad4 OTH AF: 0.00191

Alfa AF: 0.00222 Hom.: 1

Bravo AF: 0.00295

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

GeneDx

Aug 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.0
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs575593419; hg19: chr17-17627547;