rs12555727

Positions:

• chr9-32456658-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.*464C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 157,714 control chromosomes in the GnomAD database, including 2,473 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 (2391 hom., cov: 32)
  • Exomes 𝑓: 0.15 (82 hom.)
• Consequence: RIGI NM_014314.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4	c.*464C>T		3_prime_UTR_variant	18/18	ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883	c.*464C>T		3_prime_UTR_variant	18/18	1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750	c.*464C>T		3_prime_UTR_variant	20/20			ENSP00000506413.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24309 AN: 151930 Hom.: 2393 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.153 AC: 865 AN: 5664 Hom.: 82 Cov.: 0 AF XY: 0.152 AC XY: 462 AN XY: 3036

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.0919

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.0385

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.160 AC: 24315 AN: 152050 Hom.: 2391 Cov.: 32 AF XY: 0.162 AC XY: 12035 AN XY: 74310

Gnomad4 AFR AF: 0.0742

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0547

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.146

Alfa AF: 0.201 Hom.: 4365

Bravo AF: 0.145

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	-0.82
CADD	Benign	0.19
DANN	Benign	0.70

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: rs12555727; hg19: chr9-32456656;