9-32504296-T-C

Variant names:

• chr9-32504296-T-C
• rs4633144
• NM_014314.4:c.107-3357A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014314.4(RIGI):​c.107-3357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,820 control chromosomes in the GnomAD database, including 27,914 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 0.60 (27914 hom., cov: 30)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIGI	NM_014314.4	c.107-3357A>G		intron_variant	Intron 1 of 17	ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3	c.107-3357A>G		intron_variant	Intron 1 of 17	1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750.1	c.-44-3357A>G		intron_variant	Intron 3 of 19			ENSP00000506413.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91318 AN: 151702 Hom.: 27881 Cov.: 30

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.602 AC: 91393 AN: 151820 Hom.: 27914 Cov.: 30 AF XY: 0.594 AC XY: 44099 AN XY: 74192

African (AFR) AF: 0.652 AC: 26980 AN: 41372

American (AMR) AF: 0.510 AC: 7778 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2243 AN: 3466

East Asian (EAS) AF: 0.278 AC: 1435 AN: 5154

South Asian (SAS) AF: 0.622 AC: 2983 AN: 4796

European-Finnish (FIN) AF: 0.511 AC: 5371 AN: 10516

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42589 AN: 67954

Other (OTH) AF: 0.592 AC: 1246 AN: 2104

Alfa AF: 0.618 Hom.: 13693

Bravo AF: 0.599

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.043
DANN	Benign	0.22
PhyloP100		-2.9
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: rs4633144; hg19: chr9-32504294;