Variant rs55789327 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014314.4(RIGI):c.431C>T(p.Ser144Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00886 in 1,614,068 control chromosomes in the GnomAD database, including 475 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S144P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.029 ( 182 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 293 hom. )

Consequence

RIGI
NM_014314.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.313

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001844585).

BP6

Variant 9-32492531-G-A is Benign according to our data. Variant chr9-32492531-G-A is described in ClinVar as [Benign]. Clinvar id is 1169188.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIGI	NM_014314.4 linkuse as main transcript	c.431C>T	p.Ser144Phe	missense_variant	4/18	ENST00000379883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIGI	ENST00000379883.3 linkuse as main transcript	c.431C>T	p.Ser144Phe	missense_variant	4/18	1	NM_014314.4	P1	O95786-1

Frequencies

GnomAD3 genomes

AF:

0.0289

AC:

4403

AN:

152120

Hom.:

177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0870

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.0478

Gnomad SAS

AF:

0.0347

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0161

AC:

4044

AN:

251322

Hom.:

121

AF XY:

0.0152

AC XY:

2066

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.0897

Gnomad AMR exome

AF:

0.00905

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.0509

Gnomad SAS exome

AF:

0.0367

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000774

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.00675

AC:

9874

AN:

1461830

Hom.:

293

Cov.:

AF XY:

0.00726

AC XY:

5276

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0902

Gnomad4 AMR exome

AF:

0.00932

Gnomad4 ASJ exome

AF:

0.00467

Gnomad4 EAS exome

AF:

0.0483

Gnomad4 SAS exome

AF:

0.0334

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000531

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.0291

AC:

4432

AN:

152238

Hom.:

182

Cov.:

AF XY:

0.0296

AC XY:

2203

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0875

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.0481

Gnomad4 SAS

AF:

0.0345

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00747

Hom.:

Bravo

AF:

0.0320

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0792

AC:

349

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0172

AC:

2091

Asia WGS

AF:

0.0510

AC:

177

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.48

DEOGEN2

Benign

0.095

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

REVEL

Benign

0.013

Sift

Benign

0.11

Sift4G

Benign

0.13

Polyphen

0.0020

Vest4

0.045

MPC

0.12

ClinPred

0.0011

GERP RS

-2.0

Varity_R

0.14

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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