NM_014314.4:c.107-2503A>G

Variant names:

• chr9-32503442-T-C
• rs669260
• NM_014314.4:c.107-2503A>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.107-2503A>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 NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 18 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 (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIGI	NM_014314.4	c.107-2503A>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.107-2503A>G		intron_variant	Intron 1 of 17	1	NM_014314.4	ENSP00000369213.2
ENSG00000288684	ENST00000681750.1	c.-44-2503A>G		intron_variant	Intron 3 of 19			ENSP00000506413.1

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

African (AFR) AF: 0.140 AC: 5825 AN: 41498

American (AMR) AF: 0.108 AC: 1653 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3470

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5168

South Asian (SAS) AF: 0.0692 AC: 334 AN: 4826

European-Finnish (FIN) AF: 0.136 AC: 1435 AN: 10562

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10045 AN: 67968

Other (OTH) AF: 0.153 AC: 323 AN: 2110

Alfa AF: 0.146 Hom.: 5160

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
PhyloP100		0.048
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: rs669260; hg19: chr9-32503440;