NM_014314.4:c.2482-113C>T

Variant names:

• chr9-32457531-G-A
• rs17289116
• NM_014314.4:c.2482-113C>T

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.2482-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 911,234 control chromosomes in the GnomAD database, including 17,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2337 hom., cov: 30)
  • Exomes 𝑓: 0.19 (15072 hom.)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.625
• Publications: 5 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=-0.86).
• BP6: Variant 9-32457531-G-A is Benign according to our data. Variant chr9-32457531-G-A is described in ClinVar as Benign. ClinVar VariationId is 2637888.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 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.2482-113C>T		intron	N/A	NP_055129.2
	RIGI	NM_001385907.1		c.2476-113C>T		intron	N/A	NP_001372836.1
	RIGI	NM_001385913.1		c.2467-113C>T		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.2482-113C>T		intron	N/A	ENSP00000369213.2
	ENSG00000288684	ENST00000681750.1		c.2332-113C>T		intron	N/A	ENSP00000506413.1
	RIGI	ENST00000715271.1		c.2479-113C>T		intron	N/A	ENSP00000520440.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23765 AN: 150570 Hom.: 2340 Cov.: 30

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.188 AC: 143106 AN: 760564 Hom.: 15072 AF XY: 0.192 AC XY: 72800 AN XY: 379530

African (AFR) AF: 0.0620 AC: 1129 AN: 18204

American (AMR) AF: 0.109 AC: 1664 AN: 15334

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 2459 AN: 14668

East Asian (EAS) AF: 0.0665 AC: 2081 AN: 31304

South Asian (SAS) AF: 0.291 AC: 10887 AN: 37436

European-Finnish (FIN) AF: 0.193 AC: 6789 AN: 35182

Middle Eastern (MID) AF: 0.221 AC: 540 AN: 2446

European-Non Finnish (NFE) AF: 0.195 AC: 111387 AN: 570918

Other (OTH) AF: 0.176 AC: 6170 AN: 35072

GnomAD4 genome AF: 0.158 AC: 23763 AN: 150670 Hom.: 2337 Cov.: 30 AF XY: 0.159 AC XY: 11660 AN XY: 73424

African (AFR) AF: 0.0699 AC: 2870 AN: 41060

American (AMR) AF: 0.117 AC: 1774 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3470

East Asian (EAS) AF: 0.0546 AC: 281 AN: 5148

South Asian (SAS) AF: 0.318 AC: 1513 AN: 4754

European-Finnish (FIN) AF: 0.189 AC: 1892 AN: 9996

Middle Eastern (MID) AF: 0.162 AC: 47 AN: 290

European-Non Finnish (NFE) AF: 0.212 AC: 14359 AN: 67778

Other (OTH) AF: 0.144 AC: 303 AN: 2098

Alfa AF: 0.193 Hom.: 1092

Bravo AF: 0.144

Asia WGS AF: 0.173 AC: 605 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 14, 2023

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: 21. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.48
PhyloP100		0.63
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: rs17289116; hg19: chr9-32457529;