9-32469907-T-C

Position:

• chr9-32469907-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.2015-1975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,038 control chromosomes in the GnomAD database, including 9,425 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 0.34 (9425 hom., cov: 32)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4	c.2015-1975A>G		intron_variant		ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3	c.2015-1975A>G		intron_variant		1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750.1	c.1865-1975A>G		intron_variant				ENSP00000506413.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52189 AN: 151920 Hom.: 9409 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.344 AC: 52242 AN: 152038 Hom.: 9425 Cov.: 32 AF XY: 0.349 AC XY: 25930 AN XY: 74302

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.374

Alfa AF: 0.305 Hom.: 1185

Bravo AF: 0.349

Asia WGS AF: 0.487 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.66

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: rs7022323; hg19: chr9-32469905;