rs55789327

chr9-32492531-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.313

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]

ACMG classification

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	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	c.431C>T	p.Ser144Phe	missense_variant	4/18	1	NM_014314.4	P1

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4403 AN: 152120 Hom.: 177 Cov.: 32

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

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.: 31 AF XY: 0.00726 AC XY: 5276 AN XY: 727216

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.: 32 AF XY: 0.0296 AC XY: 2203 AN XY: 74448

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.: 65

Bravo AF: 0.0320

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.0792 AC: 349

ESP6500EA AF: 0.000698 AC: 6

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	10
Dann	Benign	0.48
DEOGEN2	Benign	0.095	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.013
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.0020	B
Vest4		0.045
MPC		0.12
ClinPred		0.0011	T
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

Other links and lift over

dbSNP: rs55789327; hg19: chr9-32492529; COSMIC: COSV65882655;