chr9-32492354-T-C

Variant names:

• chr9-32492354-T-C
• rs17289927
• NM_014314.4:c.571+37A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• Singleton-Merten syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Singleton-Merten dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288684 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014314.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	NM_014314.4	MANE Select	c.571+37A>G		intron	N/A	NP_055129.2
	RIGI	NM_001385907.1		c.571+37A>G		intron	N/A	NP_001372836.1
	RIGI	NM_001385913.1		c.556+37A>G		intron	N/A	NP_001372842.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	ENST00000379883.3	TSL:1 MANE Select	c.571+37A>G		intron	N/A	ENSP00000369213.2
	ENSG00000288684	ENST00000681750.1		c.421+37A>G		intron	N/A	ENSP00000506413.1
	RIGI	ENST00000715271.1		c.568+37A>G		intron	N/A	ENSP00000520440.1

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

GnomAD2 exomes AF: 0.114 AC: 28375 AN: 248800 AF XY: 0.116

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 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

African (AFR) AF: 0.0720 AC: 2405 AN: 33380

American (AMR) AF: 0.0697 AC: 3108 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5490 AN: 26038

East Asian (EAS) AF: 0.0122 AC: 485 AN: 39644

South Asian (SAS) AF: 0.0734 AC: 6313 AN: 85984

European-Finnish (FIN) AF: 0.138 AC: 7361 AN: 53298

Middle Eastern (MID) AF: 0.227 AC: 1309 AN: 5758

European-Non Finnish (NFE) AF: 0.142 AC: 157275 AN: 1109324

Other (OTH) AF: 0.132 AC: 7951 AN: 60242

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

African (AFR) AF: 0.0723 AC: 2998 AN: 41488

American (AMR) AF: 0.0985 AC: 1504 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3468

East Asian (EAS) AF: 0.0140 AC: 72 AN: 5156

South Asian (SAS) AF: 0.0686 AC: 331 AN: 4824

European-Finnish (FIN) AF: 0.137 AC: 1449 AN: 10576

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10034 AN: 67956

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.143 Hom.: 2197

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.6
DANN	Benign	0.51
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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