rs10813831

Positions:

• chr9-32526148-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014314.4(RIGI):​c.19C>T​(p.Arg7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,611,284 control chromosomes in the GnomAD database, including 50,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.23 (4233 hom., cov: 29)
  • Exomes 𝑓: 0.25 (46361 hom.)
• Consequence: RIGI NM_014314.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.258

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047461987).
• BP6: Variant 9-32526148-G-A is Benign according to our data. Variant chr9-32526148-G-A is described in ClinVar as [Benign]. Clinvar id is 1170307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4	c.19C>T	p.Arg7Cys	missense_variant	1/18	ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3	c.19C>T	p.Arg7Cys	missense_variant	1/18	1	NM_014314.4	ENSP00000369213	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35184 AN: 151598 Hom.: 4233 Cov.: 29

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0969

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.236

GnomAD3 exomes AF: 0.212 AC: 52955 AN: 249658 Hom.: 6142 AF XY: 0.214 AC XY: 28847 AN XY: 135038

Gnomad AFR exome AF: 0.238

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.104

Gnomad SAS exome AF: 0.153

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.246 AC: 359703 AN: 1459568 Hom.: 46361 Cov.: 33 AF XY: 0.244 AC XY: 177029 AN XY: 726100

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.0778

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.232 AC: 35178 AN: 151716 Hom.: 4233 Cov.: 29 AF XY: 0.228 AC XY: 16935 AN XY: 74118

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.0970

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.233

Alfa AF: 0.250 Hom.: 7044

Bravo AF: 0.229

TwinsUK AF: 0.286 AC: 1062

ALSPAC AF: 0.274 AC: 1055

ESP6500AA AF: 0.231 AC: 1018

ESP6500EA AF: 0.257 AC: 2213

ExAC AF: 0.218 AC: 26430

Asia WGS AF: 0.122 AC: 423 AN: 3478

EpiCase AF: 0.259

EpiControl AF: 0.265

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 14, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied by a panel of primary immunodeficiencies. Number of patients: 36. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.12
Sift	Benign	0.068	T
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.064
MPC		0.44
ClinPred		0.044	T
GERP RS		-2.1
Varity_R		0.18
gMVP		0.22

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: rs10813831; hg19: chr9-32526146; COSMIC: COSV65882783;