rs10813831

Variant names:

• chr9-32526148-G-A
• rs10813831
• NM_014314.4:c.19C>T

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 66 publications found

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]

RIGI Gene-Disease associations (from GenCC):

• Singleton-Merten syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Singleton-Merten dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288684 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014314.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	NM_014314.4	MANE Select	c.19C>T	p.Arg7Cys	missense	Exon 1 of 18	NP_055129.2
	RIGI	NM_001385910.1		c.-436C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_001372839.1
	RIGI	NM_001385914.1		c.-436C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_001372843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	ENST00000379883.3	TSL:1 MANE Select	c.19C>T	p.Arg7Cys	missense	Exon 1 of 18	ENSP00000369213.2
	ENSG00000288684	ENST00000681750.1		c.-45+24626C>T		intron	N/A	ENSP00000506413.1
	RIGI	ENST00000715271.1		c.19C>T	p.Arg7Cys	missense	Exon 1 of 18	ENSP00000520440.1

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

GnomAD2 exomes AF: 0.212 AC: 52955 AN: 249658 AF XY: 0.214

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 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

African (AFR) AF: 0.238 AC: 7948 AN: 33432

American (AMR) AF: 0.144 AC: 6421 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 5290 AN: 26106

East Asian (EAS) AF: 0.0778 AC: 3084 AN: 39642

South Asian (SAS) AF: 0.159 AC: 13662 AN: 86170

European-Finnish (FIN) AF: 0.231 AC: 12281 AN: 53126

Middle Eastern (MID) AF: 0.199 AC: 1144 AN: 5742

European-Non Finnish (NFE) AF: 0.266 AC: 295834 AN: 1110366

Other (OTH) AF: 0.233 AC: 14039 AN: 60308

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

African (AFR) AF: 0.234 AC: 9679 AN: 41328

American (AMR) AF: 0.193 AC: 2945 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3466

East Asian (EAS) AF: 0.0970 AC: 498 AN: 5136

South Asian (SAS) AF: 0.151 AC: 721 AN: 4778

European-Finnish (FIN) AF: 0.218 AC: 2293 AN: 10530

Middle Eastern (MID) AF: 0.186 AC: 54 AN: 290

European-Non Finnish (NFE) AF: 0.260 AC: 17662 AN: 67938

Other (OTH) AF: 0.233 AC: 489 AN: 2100

Alfa AF: 0.248 Hom.: 9674

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

Nov 14, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.26
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
PromoterAI		-0.24	Neutral
Varity_R		0.18
gMVP		0.22
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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