9-32467131-G-A

Position:

• chr9-32467131-G-A

Variant summary

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

The NM_014314.4(RIGI):​c.2185+631C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,938 control chromosomes in the GnomAD database, including 9,365 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 (9365 hom., cov: 31)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4	c.2185+631C>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.2185+631C>T		intron_variant		1	NM_014314.4	ENSP00000369213	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50820 AN: 151820 Hom.: 9362 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.335 AC: 50828 AN: 151938 Hom.: 9365 Cov.: 31 AF XY: 0.331 AC XY: 24611 AN XY: 74242

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.345

Alfa AF: 0.412 Hom.: 17314

Bravo AF: 0.323

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.95

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: rs10813821; hg19: chr9-32467129;