9-32508588-C-G

Variant names:

• chr9-32508588-C-G
• rs582509
• NM_014314.4:c.107-7649G>C

Variant summary

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

The NM_014314.4(RIGI):​c.107-7649G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,872 control chromosomes in the GnomAD database, including 13,120 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 (13120 hom., cov: 30)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIGI	NM_014314.4	c.107-7649G>C		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.107-7649G>C		intron_variant	Intron 1 of 17	1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750.1	c.-44-7649G>C		intron_variant	Intron 3 of 19			ENSP00000506413.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61257 AN: 151754 Hom.: 13115 Cov.: 30

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.403 AC: 61269 AN: 151872 Hom.: 13120 Cov.: 30 AF XY: 0.400 AC XY: 29715 AN XY: 74210

African (AFR) AF: 0.288 AC: 11928 AN: 41424

American (AMR) AF: 0.379 AC: 5780 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1101 AN: 5156

South Asian (SAS) AF: 0.531 AC: 2550 AN: 4802

European-Finnish (FIN) AF: 0.388 AC: 4089 AN: 10550

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 32992 AN: 67902

Other (OTH) AF: 0.398 AC: 839 AN: 2110

Alfa AF: 0.301 Hom.: 782

Bravo AF: 0.392

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.46
PhyloP100		0.20
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: rs582509; hg19: chr9-32508586;