rs592515

Variant names:

• chr9-32488561-T-A
• rs592515
• NM_014314.4:c.953+173A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-32488561-T-A
• chr9-32488561-T-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.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
• Publications: 3 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=-0.9).
• 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 rank	MANE	Protein	UniProt
RIGI	NM_014314.4	c.953+173A>T		intron_variant	Intron 7 of 17	ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3	c.953+173A>T		intron_variant	Intron 7 of 17	1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750.1	c.803+173A>T		intron_variant	Intron 9 of 19			ENSP00000506413.1

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

African (AFR) AF: 0.550 AC: 22804 AN: 41492

American (AMR) AF: 0.382 AC: 5835 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1392 AN: 3472

East Asian (EAS) AF: 0.233 AC: 1209 AN: 5186

South Asian (SAS) AF: 0.518 AC: 2500 AN: 4822

European-Finnish (FIN) AF: 0.325 AC: 3424 AN: 10544

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29202 AN: 67956

Other (OTH) AF: 0.424 AC: 891 AN: 2102

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
PhyloP100		0.41
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: rs592515; hg19: chr9-32488559;