rs7865082

Variant names:

• chr9-32457560-A-G
• rs7865082
• NM_014314.4:c.2482-142T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014314.4(RIGI):​c.2482-142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 530,590 control chromosomes in the GnomAD database, including 31,494 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6837 hom., cov: 30)
  • Exomes 𝑓: 0.43 (24657 hom.)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 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.2482-142T>C		intron	N/A	NP_055129.2
	RIGI	NM_001385907.1		c.2476-142T>C		intron	N/A	NP_001372836.1
	RIGI	NM_001385913.1		c.2467-142T>C		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.2482-142T>C		intron	N/A	ENSP00000369213.2
	ENSG00000288684	ENST00000681750.1		c.2332-142T>C		intron	N/A	ENSP00000506413.1
	RIGI	ENST00000715271.1		c.2479-142T>C		intron	N/A	ENSP00000520440.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 42367 AN: 148390 Hom.: 6833 Cov.: 30

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.426 AC: 162715 AN: 382122 Hom.: 24657 AF XY: 0.425 AC XY: 82441 AN XY: 194056

African (AFR) AF: 0.190 AC: 1351 AN: 7098

American (AMR) AF: 0.424 AC: 3837 AN: 9058

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 4492 AN: 9460

East Asian (EAS) AF: 0.529 AC: 11856 AN: 22414

South Asian (SAS) AF: 0.356 AC: 6524 AN: 18350

European-Finnish (FIN) AF: 0.427 AC: 8415 AN: 19690

Middle Eastern (MID) AF: 0.401 AC: 525 AN: 1310

European-Non Finnish (NFE) AF: 0.427 AC: 117647 AN: 275524

Other (OTH) AF: 0.420 AC: 8068 AN: 19218

GnomAD4 genome AF: 0.285 AC: 42378 AN: 148468 Hom.: 6837 Cov.: 30 AF XY: 0.287 AC XY: 20774 AN XY: 72324

African (AFR) AF: 0.115 AC: 4643 AN: 40210

American (AMR) AF: 0.327 AC: 4881 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1300 AN: 3436

East Asian (EAS) AF: 0.532 AC: 2708 AN: 5090

South Asian (SAS) AF: 0.251 AC: 1180 AN: 4692

European-Finnish (FIN) AF: 0.327 AC: 3224 AN: 9866

Middle Eastern (MID) AF: 0.333 AC: 94 AN: 282

European-Non Finnish (NFE) AF: 0.348 AC: 23314 AN: 67014

Other (OTH) AF: 0.337 AC: 690 AN: 2048

Alfa AF: 0.327 Hom.: 4940

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.58
PhyloP100		0.27
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: rs7865082; hg19: chr9-32457558; COSMIC: COSV59377278; COSMIC: COSV59377278;