rs621277

Variant names:

• chr9-32516866-G-A
• rs621277
• NM_014314.4:c.106+9195C>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.106+9195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,040 control chromosomes in the GnomAD database, including 23,699 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 0.55 (23699 hom., cov: 32)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.625 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.106+9195C>T		intron	N/A	NP_055129.2
	RIGI	NM_001385907.1		c.106+9195C>T		intron	N/A	NP_001372836.1	A0AAQ5BIG4
	RIGI	NM_001385913.1		c.106+9195C>T		intron	N/A	NP_001372842.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	ENST00000379883.3	TSL:1 MANE Select	c.106+9195C>T		intron	N/A	ENSP00000369213.2	O95786-1
	ENSG00000288684	ENST00000681750.1		c.-44-15927C>T		intron	N/A	ENSP00000506413.1	A0A7P0TB70
	RIGI	ENST00000715271.1		c.106+9195C>T		intron	N/A	ENSP00000520440.1	A0AAQ5BIF4

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83787 AN: 151922 Hom.: 23685 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.551 AC: 83836 AN: 152040 Hom.: 23699 Cov.: 32 AF XY: 0.547 AC XY: 40633 AN XY: 74320

African (AFR) AF: 0.455 AC: 18861 AN: 41458

American (AMR) AF: 0.502 AC: 7665 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3468

East Asian (EAS) AF: 0.357 AC: 1845 AN: 5166

South Asian (SAS) AF: 0.631 AC: 3040 AN: 4820

European-Finnish (FIN) AF: 0.516 AC: 5447 AN: 10560

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42796 AN: 67974

Other (OTH) AF: 0.560 AC: 1180 AN: 2108

Alfa AF: 0.607 Hom.: 90276

Bravo AF: 0.541

Asia WGS AF: 0.486 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.94
PhyloP100		-0.71
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: rs621277; hg19: chr9-32516864;