rs10738890

Variant names:

• chr9-32458083-T-C
• rs10738890
• NM_014314.4:c.2482-665A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-32458083-T-C
• chr9-32458083-T-G

Variant summary

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

The NM_014314.4(RIGI):​c.2482-665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,066 control chromosomes in the GnomAD database, including 8,506 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 0.32 (8506 hom., cov: 32)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 9 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 (AMR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIGI	NM_014314.4	c.2482-665A>G		intron_variant	Intron 17 of 17	ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3	c.2482-665A>G		intron_variant	Intron 17 of 17	1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750.1	c.2332-665A>G		intron_variant	Intron 19 of 19			ENSP00000506413.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48704 AN: 151948 Hom.: 8495 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.320 AC: 48728 AN: 152066 Hom.: 8506 Cov.: 32 AF XY: 0.317 AC XY: 23574 AN XY: 74306

African (AFR) AF: 0.179 AC: 7423 AN: 41508

American (AMR) AF: 0.400 AC: 6108 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1162 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1963 AN: 5162

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4828

European-Finnish (FIN) AF: 0.316 AC: 3338 AN: 10568

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26276 AN: 67942

Other (OTH) AF: 0.349 AC: 737 AN: 2110

Alfa AF: 0.371 Hom.: 17202

Bravo AF: 0.323

Asia WGS AF: 0.333 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.72
PhyloP100		0.12
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: rs10738890; hg19: chr9-32458081; COSMIC: COSV59384458; COSMIC: COSV59384458;