rs12006123

chr9-32456019-G-Achr9-32456019-G-T

Variant summary

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

The NM_014314.4(RIGI):c.*1103C>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 0.207 in 152,046 control chromosomes in the GnomAD database, including 3,538 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 0.21 (3538 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: RIGI NM_014314.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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=-0.89).
• 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	UniProt
RIGI	NM_014314.4	c.*1103C>T		3_prime_UTR_variant	18/18	ENST00000379883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIGI	ENST00000379883.3	c.*1103C>T		3_prime_UTR_variant	18/18	1	NM_014314.4	P1
RIGI	ENST00000379868.6	c.*1103C>T		3_prime_UTR_variant	17/17	5
RIGI	ENST00000679665.1	c.*1103C>T		3_prime_UTR_variant	19/19
RIGI	ENST00000679771.1	c.*3304C>T		3_prime_UTR_variant, NMD_transcript_variant	17/17

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31488 AN: 151922 Hom.: 3528 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 FIN exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.207 AC: 31533 AN: 152040 Hom.: 3538 Cov.: 32 AF XY: 0.208 AC XY: 15447 AN XY: 74308

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.0585

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.177

Alfa AF: 0.201 Hom.: 5474

Bravo AF: 0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.70
Dann	Benign	0.64

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: rs12006123; hg19: chr9-32456017;