rs7865082

chr9-32457560-A-G

Variant summary

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

The NM_014314.4(RIGI):c.2482-142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 530,590 control chromosomes in the GnomAD database, including 31,494 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 0.29 (6837 hom., cov: 30)
  • Exomes 𝑓: 0.43 (24657 hom.)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIGI	NM_014314.4	c.2482-142T>C		intron_variant		ENST00000379883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIGI	ENST00000379883.3	c.2482-142T>C		intron_variant		1	NM_014314.4	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 42367 AN: 148390 Hom.: 6833 Cov.: 30

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.426 AC: 162715 AN: 382122 Hom.: 24657 AF XY: 0.425 AC XY: 82441 AN XY: 194056

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.529

Gnomad4 SAS exome AF: 0.356

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.427

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.285 AC: 42378 AN: 148468 Hom.: 6837 Cov.: 30 AF XY: 0.287 AC XY: 20774 AN XY: 72324

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.337

Alfa AF: 0.327 Hom.: 4477

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.0
Dann	Benign	0.58

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: rs7865082; hg19: chr9-32457558; COSMIC: COSV59377278; COSMIC: COSV59377278;