Variant chr9-32457247-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_014314.4(RIGI):c.2653C>T(p.Pro885Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000894 in 1,614,070 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 2 hom. )

Consequence

RIGI
NM_014314.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.61

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 -12 ACMG points.

BP6

Variant 9-32457247-G-A is Benign according to our data. Variant chr9-32457247-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1017102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 75 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4 linkuse as main transcript	c.2653C>T	p.Pro885Ser	missense_variant	18/18	ENST00000379883.3	NP_055129.2	O95786-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3 linkuse as main transcript	c.2653C>T	p.Pro885Ser	missense_variant	18/18	1	NM_014314.4	ENSP00000369213.2		O95786-1
ENSG00000288684	ENST00000681750.1 linkuse as main transcript	c.2503C>T	p.Pro835Ser	missense_variant	20/20			ENSP00000506413.1		A0A7P0TB70

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000418

AC:

105

AN:

251450

Hom.:

AF XY:

0.000456

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.000651

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000936

AC:

1368

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

713

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.000449

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000493

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000725

Hom.:

Bravo

AF:

0.000446

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000371

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	RIGI: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

T;D

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Uncertain

-0.062

MutationAssessor

Pathogenic

3.1

.;M

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.8

D;D

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.64

MVP

0.85

MPC

0.54

ClinPred

0.38

GERP RS

4.9

Varity_R

0.91

gMVP

0.78

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