rs10738889

chr9-32458055-A-Gchr9-32458055-A-T

Variant summary

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

The NM_014314.4(RIGI):c.2482-637T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,038 control chromosomes in the GnomAD database, including 8,862 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 0.33 (8862 hom., cov: 32)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIGI	NM_014314.4	c.2482-637T>C		intron_variant		ENST00000379883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIGI	ENST00000379883.3	c.2482-637T>C		intron_variant		1	NM_014314.4	P1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50560 AN: 151918 Hom.: 8851 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.333 AC: 50583 AN: 152038 Hom.: 8862 Cov.: 32 AF XY: 0.329 AC XY: 24436 AN XY: 74304

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.356

Alfa AF: 0.380 Hom.: 11440

Bravo AF: 0.337

Asia WGS AF: 0.326 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.50
Dann	Benign	0.67

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: rs10738889; hg19: chr9-32458053; COSMIC: COSV59384454; COSMIC: COSV59384454;