rs12555727

Variant names:

• chr9-32456658-G-A
• rs12555727
• NM_014314.4:c.*464C>T

Variant summary

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

The NM_014314.4(RIGI):​c.*464C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 157,714 control chromosomes in the GnomAD database, including 2,473 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 0.16 (2391 hom., cov: 32)
  • Exomes 𝑓: 0.15 (82 hom.)
• Consequence: RIGI NM_014314.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• 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), G2P, Ambry Genetics
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	NM_014314.4	MANE Select	c.*464C>T		3_prime_UTR	Exon 18 of 18	NP_055129.2
	RIGI	NM_001385907.1		c.*464C>T		3_prime_UTR	Exon 18 of 18	NP_001372836.1	A0AAQ5BIG4
	RIGI	NM_001385913.1		c.*464C>T		3_prime_UTR	Exon 18 of 18	NP_001372842.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	ENST00000379883.3	TSL:1 MANE Select	c.*464C>T		3_prime_UTR	Exon 18 of 18	ENSP00000369213.2	O95786-1
	ENSG00000288684	ENST00000681750.1		c.*464C>T		3_prime_UTR	Exon 20 of 20	ENSP00000506413.1	A0A7P0TB70
	RIGI	ENST00000715271.1		c.*464C>T		3_prime_UTR	Exon 18 of 18	ENSP00000520440.1	A0AAQ5BIF4

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24309 AN: 151930 Hom.: 2393 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.153 AC: 865 AN: 5664 Hom.: 82 Cov.: 0 AF XY: 0.152 AC XY: 462 AN XY: 3036

African (AFR) AF: 0.0313 AC: 1 AN: 32

American (AMR) AF: 0.0919 AC: 121 AN: 1316

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6 AN: 26

East Asian (EAS) AF: 0.0385 AC: 7 AN: 182

South Asian (SAS) AF: 0.258 AC: 161 AN: 624

European-Finnish (FIN) AF: 0.173 AC: 9 AN: 52

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.165 AC: 536 AN: 3240

Other (OTH) AF: 0.122 AC: 23 AN: 188

GnomAD4 genome AF: 0.160 AC: 24315 AN: 152050 Hom.: 2391 Cov.: 32 AF XY: 0.162 AC XY: 12035 AN XY: 74310

African (AFR) AF: 0.0742 AC: 3077 AN: 41494

American (AMR) AF: 0.117 AC: 1789 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.0547 AC: 282 AN: 5156

South Asian (SAS) AF: 0.319 AC: 1538 AN: 4816

European-Finnish (FIN) AF: 0.204 AC: 2156 AN: 10574

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14390 AN: 67956

Other (OTH) AF: 0.146 AC: 308 AN: 2114

Alfa AF: 0.200 Hom.: 5410

Bravo AF: 0.145

Asia WGS AF: 0.173 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.19
DANN	Benign	0.70
PhyloP100		-2.1
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: rs12555727; hg19: chr9-32456656;