Variant 9-32457191-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014314.4(RIGI):c.2709A>G(p.Thr903=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 1,612,948 control chromosomes in the GnomAD database, including 5,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 462 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5223 hom. )

Consequence

RIGI
NM_014314.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.76

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 9-32457191-T-C is Benign according to our data. Variant chr9-32457191-T-C is described in ClinVar as [Benign]. Clinvar id is 1168035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4 linkuse as main transcript	c.2709A>G	p.Thr903=	synonymous_variant	18/18	ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3 linkuse as main transcript	c.2709A>G	p.Thr903=	synonymous_variant	18/18	1	NM_014314.4	ENSP00000369213	P1	O95786-1

Frequencies

GnomAD3 genomes

AF:

0.0643

AC:

9778

AN:

152078

Hom.:

463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0491

Gnomad FIN

AF:

0.0895

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0870

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0825

AC:

20748

AN:

251386

Hom.:

1280

AF XY:

0.0790

AC XY:

10730

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.0410

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0577

Gnomad FIN exome

AF:

0.0916

Gnomad NFE exome

AF:

0.0836

Gnomad OTH exome

AF:

0.0722

GnomAD4 exome

AF:

0.0791

AC:

115556

AN:

1460752

Hom.:

5223

Cov.:

AF XY:

0.0785

AC XY:

57058

AN XY:

726692

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.0412

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0604

Gnomad4 FIN exome

AF:

0.0955

Gnomad4 NFE exome

AF:

0.0824

Gnomad4 OTH exome

AF:

0.0683

GnomAD4 genome

AF:

0.0643

AC:

9779

AN:

152196

Hom.:

462

Cov.:

AF XY:

0.0636

AC XY:

4735

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0492

Gnomad4 FIN

AF:

0.0895

Gnomad4 NFE

AF:

0.0870

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0786

Hom.:

375

Bravo

AF:

0.0643

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0767

EpiControl

AF:

0.0741

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

RIGI-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.7

DANN

Benign

0.52

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