rs10738889

Variant names:

• chr9-32458055-A-G
• rs10738889
• NM_014314.4:c.2482-637T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-32458055-A-G
• chr9-32458055-A-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.2482-637T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,038 control chromosomes in the GnomAD database, including 8,862 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 0.33 (8862 hom., cov: 32)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 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.2482-637T>C		intron	N/A	NP_055129.2
	RIGI	NM_001385907.1		c.2476-637T>C		intron	N/A	NP_001372836.1	A0AAQ5BIG4
	RIGI	NM_001385913.1		c.2467-637T>C		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.2482-637T>C		intron	N/A	ENSP00000369213.2	O95786-1
	ENSG00000288684	ENST00000681750.1		c.2332-637T>C		intron	N/A	ENSP00000506413.1	A0A7P0TB70
	RIGI	ENST00000715271.1		c.2479-637T>C		intron	N/A	ENSP00000520440.1	A0AAQ5BIF4

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50560 AN: 151918 Hom.: 8851 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.333 AC: 50583 AN: 152038 Hom.: 8862 Cov.: 32 AF XY: 0.329 AC XY: 24436 AN XY: 74304

African (AFR) AF: 0.221 AC: 9163 AN: 41486

American (AMR) AF: 0.405 AC: 6191 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1160 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1959 AN: 5158

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4816

European-Finnish (FIN) AF: 0.316 AC: 3337 AN: 10572

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26300 AN: 67950

Other (OTH) AF: 0.356 AC: 752 AN: 2114

Alfa AF: 0.369 Hom.: 30016

Bravo AF: 0.337

Asia WGS AF: 0.326 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.50
DANN	Benign	0.67
PhyloP100		-0.75
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: rs10738889; hg19: chr9-32458053; COSMIC: COSV59384454; COSMIC: COSV59384454;