rs6476363

chr9-32491242-C-T

Variant summary

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

The NM_014314.4(RIGI):c.691+59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,580,764 control chromosomes in the GnomAD database, including 235,088 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 0.48 (18462 hom., cov: 31)
  • Exomes 𝑓: 0.54 (216626 hom.)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIGI	NM_014314.4	c.691+59G>A		intron_variant		ENST00000379883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIGI	ENST00000379883.3	c.691+59G>A		intron_variant		1	NM_014314.4	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73256 AN: 151732 Hom.: 18465 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.544 AC: 777190 AN: 1428914 Hom.: 216626 AF XY: 0.546 AC XY: 387984 AN XY: 710764

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.614

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.533

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.483 AC: 73274 AN: 151850 Hom.: 18462 Cov.: 31 AF XY: 0.475 AC XY: 35260 AN XY: 74196

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.509

Alfa AF: 0.555 Hom.: 10768

Bravo AF: 0.473

Asia WGS AF: 0.380 AC: 1323 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	2.1
Dann	Benign	0.20

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: rs6476363; hg19: chr9-32491240; COSMIC: COSV65882136;