rs12006123

Variant names:

• chr9-32456019-G-A
• rs12006123
• NM_014314.4:c.*1103C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-32456019-G-A
• chr9-32456019-G-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.*1103C>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 0.207 in 152,046 control chromosomes in the GnomAD database, including 3,538 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 0.21 (3538 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: RIGI NM_014314.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 15 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=-0.89).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	NM_014314.4	MANE Select	c.*1103C>T		3_prime_UTR	Exon 18 of 18	NP_055129.2
	RIGI	NM_001385907.1		c.*1103C>T		3_prime_UTR	Exon 18 of 18	NP_001372836.1
	RIGI	NM_001385913.1		c.*1103C>T		3_prime_UTR	Exon 18 of 18	NP_001372842.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	ENST00000379883.3	TSL:1 MANE Select	c.*1103C>T		3_prime_UTR	Exon 18 of 18	ENSP00000369213.2
	ENSG00000288684	ENST00000681750.1		c.*1103C>T		3_prime_UTR	Exon 20 of 20	ENSP00000506413.1
	RIGI	ENST00000679771.1		n.*3304C>T		non_coding_transcript_exon	Exon 17 of 17	ENSP00000505015.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31488 AN: 151922 Hom.: 3528 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.207 AC: 31533 AN: 152040 Hom.: 3538 Cov.: 32 AF XY: 0.208 AC XY: 15447 AN XY: 74308

African (AFR) AF: 0.237 AC: 9836 AN: 41466

American (AMR) AF: 0.136 AC: 2080 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3470

East Asian (EAS) AF: 0.0585 AC: 301 AN: 5148

South Asian (SAS) AF: 0.320 AC: 1539 AN: 4814

European-Finnish (FIN) AF: 0.203 AC: 2144 AN: 10548

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14469 AN: 67974

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.207 Hom.: 13140

Bravo AF: 0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
DANN	Benign	0.64
PhyloP100		-1.9
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: rs12006123; hg19: chr9-32456017;