9-32525917-C-G

Variant names:

• chr9-32525917-C-G
• rs3824456
• NM_014314.4:c.106+144G>C

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000288684 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.250

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

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.226

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3824456; hg19: chr9-32525915;