rs1133071

chr9-32455676-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.*1446T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 150,044 control chromosomes in the GnomAD database, including 8,077 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 0.32 (8077 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: RIGI NM_014314.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIGI	NM_014314.4	c.*1446T>C		3_prime_UTR_variant	18/18	ENST00000379883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIGI	ENST00000379883.3	c.*1446T>C		3_prime_UTR_variant	18/18	1	NM_014314.4	P1
RIGI	ENST00000379868.6	c.*1446T>C		3_prime_UTR_variant	17/17	5
RIGI	ENST00000679665.1	c.*1446T>C		3_prime_UTR_variant	19/19
RIGI	ENST00000679771.1	c.*3647T>C		3_prime_UTR_variant, NMD_transcript_variant	17/17

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48300 AN: 149950 Hom.: 8062 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0645

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.261

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.322 AC: 48363 AN: 150044 Hom.: 8077 Cov.: 31 AF XY: 0.321 AC XY: 23555 AN XY: 73320

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.0646

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.261

Alfa AF: 0.316 Hom.: 1805

Bravo AF: 0.317

Asia WGS AF: 0.223 AC: 775 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.88
Dann	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1133071; hg19: chr9-32455674; COSMIC: COSV59384443;