rs3739674

Positions:

• chr9-32526235-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 9-32526235-G-C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,290,604 control chromosomes in the GnomAD database, including 237,030 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 0.57 (24720 hom., cov: 29)
  • Exomes 𝑓: 0.61 (212310 hom.)
• Consequence: RIGI NM_014314.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4			upstream_gene_variant		ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3			upstream_gene_variant		1	NM_014314.4	ENSP00000369213	P1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85988 AN: 151554 Hom.: 24706 Cov.: 29

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.608 AC: 692262 AN: 1138932 Hom.: 212310 Cov.: 14 AF XY: 0.611 AC XY: 350457 AN XY: 574020

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.532

Gnomad4 NFE exome AF: 0.626

Gnomad4 OTH exome AF: 0.598

GnomAD4 genome AF: 0.567 AC: 86027 AN: 151672 Hom.: 24720 Cov.: 29 AF XY: 0.563 AC XY: 41740 AN XY: 74086

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.578

Alfa AF: 0.604 Hom.: 3475

Bravo AF: 0.560

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs3739674; hg19: chr9-32526233; COSMIC: COSV65884177; COSMIC: COSV65884177;