rs17289116

Positions:

• chr9-32457531-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014314.4(RIGI):​c.2482-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 911,234 control chromosomes in the GnomAD database, including 17,409 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 0.16 (2337 hom., cov: 30)
  • Exomes 𝑓: 0.19 (15072 hom.)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625

Genes affected

RIGI (HGNC:19102): (RNA sensor RIG-I) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases which are implicated in a number of cellular processes involving RNA binding and alteration of RNA secondary structure. This gene encodes a protein containing RNA helicase-DEAD box protein motifs and a caspase recruitment domain (CARD). It is involved in viral double-stranded (ds) RNA recognition and the regulation of the antiviral innate immune response. Mutations in this gene are associated with Singleton-Merten syndrome 2. [provided by RefSeq, Aug 2020]

ENSG00000288684 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4	c.2482-113C>T		intron_variant		ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3	c.2482-113C>T		intron_variant		1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750.1	c.2332-113C>T		intron_variant				ENSP00000506413.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23765 AN: 150570 Hom.: 2340 Cov.: 30

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.188 AC: 143106 AN: 760564 Hom.: 15072 AF XY: 0.192 AC XY: 72800 AN XY: 379530

Gnomad4 AFR exome AF: 0.0620

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.0665

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.158 AC: 23763 AN: 150670 Hom.: 2337 Cov.: 30 AF XY: 0.159 AC XY: 11660 AN XY: 73424

Gnomad4 AFR AF: 0.0699

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0546

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.144

Alfa AF: 0.191 Hom.: 605

Bravo AF: 0.144

Asia WGS AF: 0.173 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.48

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: rs17289116; hg19: chr9-32457529;