9-32523739-T-C

Variant names:

• chr9-32523739-T-C
• rs11795343
• NM_014314.4:c.106+2322A>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.106+2322A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,768 control chromosomes in the GnomAD database, including 12,709 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 0.40 (12709 hom., cov: 31)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697
• Publications: 60 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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIGI	NM_014314.4	c.106+2322A>G		intron_variant	Intron 1 of 17	ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3	c.106+2322A>G		intron_variant	Intron 1 of 17	1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750.1	c.-44-22800A>G		intron_variant	Intron 3 of 19			ENSP00000506413.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61276 AN: 151650 Hom.: 12695 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.404 AC: 61317 AN: 151768 Hom.: 12709 Cov.: 31 AF XY: 0.399 AC XY: 29558 AN XY: 74138

African (AFR) AF: 0.490 AC: 20259 AN: 41348

American (AMR) AF: 0.307 AC: 4683 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1372 AN: 3470

East Asian (EAS) AF: 0.245 AC: 1254 AN: 5126

South Asian (SAS) AF: 0.260 AC: 1254 AN: 4826

European-Finnish (FIN) AF: 0.352 AC: 3706 AN: 10516

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27447 AN: 67916

Other (OTH) AF: 0.409 AC: 863 AN: 2108

Alfa AF: 0.404 Hom.: 39924

Bravo AF: 0.403

Asia WGS AF: 0.281 AC: 977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.5
DANN	Benign	0.88
PhyloP100		-0.70
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: rs11795343; hg19: chr9-32523737; COSMIC: COSV65882702;