9-32503442-T-C

Position:

• chr9-32503442-T-C

Variant summary

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

The ENST00000379883.3(RIGI):​c.107-2503A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,092 control chromosomes in the GnomAD database, including 1,482 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 0.14 (1482 hom., cov: 31)
• Consequence: RIGI ENST00000379883.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIGI	NM_014314.4	c.107-2503A>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.107-2503A>G		intron_variant		1	NM_014314.4	ENSP00000369213	P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20650 AN: 151974 Hom.: 1480 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.136 AC: 20676 AN: 152092 Hom.: 1482 Cov.: 31 AF XY: 0.133 AC XY: 9876 AN XY: 74376

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.0692

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.153

Alfa AF: 0.148 Hom.: 3578

Bravo AF: 0.134

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.6
DANN	Benign	0.47

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: rs669260; hg19: chr9-32503440;