9-32480253-A-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014314.4(RIGI):c.1740T>A(p.Asp580Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,609,856 control chromosomes in the GnomAD database, including 14,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.10 ( 999 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13152 hom. )

Consequence

RIGI
NM_014314.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.01

Variant links:

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 links:

ENSG00000288684 (HGNC:):

ENSG00000288684 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015563965).

BP6

Variant 9-32480253-A-T is Benign according to our data. Variant chr9-32480253-A-T is described in ClinVar as [Benign]. Clinvar id is 1168118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIGI	NM_014314.4 link	c.1740T>A	p.Asp580Glu	missense_variant	Exon 12 of 18	ENST00000379883.3	NP_055129.2	O95786-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3 link	c.1740T>A	p.Asp580Glu	missense_variant	Exon 12 of 18	1	NM_014314.4	ENSP00000369213.2		O95786-1
ENSG00000288684	ENST00000681750.1 link	c.1590T>A	p.Asp530Glu	missense_variant	Exon 14 of 20			ENSP00000506413.1		A0A7P0TB70

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15586

AN:

152134

Hom.:

1000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.0878

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.0629

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.109

AC:

27302

AN:

251010

Hom.:

1917

AF XY:

0.112

AC XY:

15160

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0255

Gnomad AMR exome

AF:

0.0585

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.00881

Gnomad SAS exome

AF:

0.0623

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.129

AC:

187427

AN:

1457604

Hom.:

13152

Cov.:

AF XY:

0.128

AC XY:

92725

AN XY:

724696

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.0634

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.00974

Gnomad4 SAS exome

AF:

0.0668

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.102

AC:

15582

AN:

152252

Hom.:

999

Cov.:

AF XY:

0.100

AC XY:

7451

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0309

Gnomad4 AMR

AF:

0.0877

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.0133

Gnomad4 SAS

AF:

0.0628

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.123

Hom.:

475

Bravo

AF:

0.0964

TwinsUK

AF:

0.129

AC:

478

ALSPAC

AF:

0.142

AC:

549

ESP6500AA

AF:

0.0322

AC:

142

ESP6500EA

AF:

0.147

AC:

1268

ExAC

AF:

0.111

AC:

13445

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

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 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Singleton-Merten syndrome 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

.;M

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.090

Sift

Benign

0.056

T;T

Sift4G

Uncertain

0.025

D;D

Polyphen

0.82

.;P

Vest4

0.092

MutPred

0.10

.;Loss of helix (P = 0.0626);

MPC

0.16

ClinPred

0.030

GERP RS

4.7

Varity_R

0.26

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over