chr9-32525917-C-G

Variant names:

• chr9-32525917-C-G
• rs3824456
• NM_014314.4:c.106+144G>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.106+144G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 717,116 control chromosomes in the GnomAD database, including 23,979 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 0.25 (5082 hom., cov: 32)
  • Exomes 𝑓: 0.25 (18897 hom.)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595
• Publications: 12 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIGI	NM_014314.4	c.106+144G>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.106+144G>C		intron_variant	Intron 1 of 17	1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750.1	c.-45+24857G>C		intron_variant	Intron 3 of 19			ENSP00000506413.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38197 AN: 152000 Hom.: 5063 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.250 AC: 141435 AN: 564996 Hom.: 18897 AF XY: 0.259 AC XY: 78373 AN XY: 302748

African (AFR) AF: 0.293 AC: 4449 AN: 15186

American (AMR) AF: 0.250 AC: 7547 AN: 30194

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 4158 AN: 17940

East Asian (EAS) AF: 0.294 AC: 9012 AN: 30672

South Asian (SAS) AF: 0.405 AC: 24072 AN: 59426

European-Finnish (FIN) AF: 0.165 AC: 5715 AN: 34686

Middle Eastern (MID) AF: 0.248 AC: 911 AN: 3666

European-Non Finnish (NFE) AF: 0.227 AC: 78084 AN: 343298

Other (OTH) AF: 0.250 AC: 7487 AN: 29928

GnomAD4 genome AF: 0.251 AC: 38257 AN: 152120 Hom.: 5082 Cov.: 32 AF XY: 0.251 AC XY: 18692 AN XY: 74356

African (AFR) AF: 0.301 AC: 12484 AN: 41490

American (AMR) AF: 0.233 AC: 3561 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 793 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1555 AN: 5160

South Asian (SAS) AF: 0.418 AC: 2017 AN: 4828

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10582

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15351 AN: 67984

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.243 Hom.: 575

Bravo AF: 0.255

Asia WGS AF: 0.326 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.64
PhyloP100		-0.59
PromoterAI		-0.10	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3824456; hg19: chr9-32525915;