9-32492354-T-C

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.571+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,610,292 control chromosomes in the GnomAD database, including 14,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1143 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13560 hom.)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.844

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 (BayesDel_noAF=-0.97).
• BP6: Variant 9-32492354-T-C is Benign according to our data. Variant chr9-32492354-T-C is described in ClinVar as [Benign]. Clinvar id is 2688507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIGI	NM_014314.4	c.571+37A>G		intron_variant		ENST00000379883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIGI	ENST00000379883.3	c.571+37A>G		intron_variant		1	NM_014314.4	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17651 AN: 151934 Hom.: 1142 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.0688

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.114 AC: 28375 AN: 248800 Hom.: 1965 AF XY: 0.116 AC XY: 15672 AN XY: 134530

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.0641

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.0103

Gnomad SAS exome AF: 0.0686

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.131 AC: 191697 AN: 1458240 Hom.: 13560 Cov.: 30 AF XY: 0.131 AC XY: 94911 AN XY: 725292

Gnomad4 AFR exome AF: 0.0720

Gnomad4 AMR exome AF: 0.0697

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.0122

Gnomad4 SAS exome AF: 0.0734

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.116 AC: 17665 AN: 152052 Hom.: 1143 Cov.: 32 AF XY: 0.114 AC XY: 8465 AN XY: 74326

Gnomad4 AFR AF: 0.0723

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.0140

Gnomad4 SAS AF: 0.0686

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.142

Alfa AF: 0.147 Hom.: 1812

Bravo AF: 0.112

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.6
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs17289927; hg19: chr9-32492352; COSMIC: COSV65883081;