rs592515

Positions:

• chr9-32488561-T-A
• chr9-32488561-T-C

Variant summary

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

The NM_014314.4(RIGI):​c.953+173A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,058 control chromosomes in the GnomAD database, including 15,511 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 0.45 (15511 hom., cov: 32)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4	c.953+173A>T		intron_variant		ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3	c.953+173A>T		intron_variant		1	NM_014314.4	ENSP00000369213	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67707 AN: 151940 Hom.: 15495 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.446 AC: 67758 AN: 152058 Hom.: 15511 Cov.: 32 AF XY: 0.440 AC XY: 32739 AN XY: 74360

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.424

Alfa AF: 0.285 Hom.: 626

Bravo AF: 0.448

Asia WGS AF: 0.373 AC: 1295 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.63

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: rs592515; hg19: chr9-32488559;