NM_014314.4:c.2337+2153C>G

Variant names:

• chr9-32464137-G-C
• rs9695310
• NM_014314.4:c.2337+2153C>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.2337+2153C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 150,748 control chromosomes in the GnomAD database, including 20,686 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 0.52 (20686 hom., cov: 27)
• Consequence: RIGI NM_014314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014314.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	NM_014314.4	MANE Select	c.2337+2153C>G		intron	N/A	NP_055129.2
	LOC101060445	NR_197444.1		n.5096G>C		non_coding_transcript_exon	Exon 1 of 1
	RIGI	NM_001385907.1		c.2331+2153C>G		intron	N/A	NP_001372836.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIGI	ENST00000379883.3	TSL:1 MANE Select	c.2337+2153C>G		intron	N/A	ENSP00000369213.2
	ENSG00000288684	ENST00000681750.1		c.2187+2153C>G		intron	N/A	ENSP00000506413.1
	RIGI	ENST00000715271.1		c.2334+2153C>G		intron	N/A	ENSP00000520440.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78271 AN: 150628 Hom.: 20654 Cov.: 27

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.520 AC: 78347 AN: 150748 Hom.: 20686 Cov.: 27 AF XY: 0.517 AC XY: 38008 AN XY: 73578

African (AFR) AF: 0.601 AC: 24694 AN: 41080

American (AMR) AF: 0.504 AC: 7648 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2148 AN: 3462

East Asian (EAS) AF: 0.324 AC: 1603 AN: 4944

South Asian (SAS) AF: 0.547 AC: 2598 AN: 4748

European-Finnish (FIN) AF: 0.435 AC: 4521 AN: 10402

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.492 AC: 33308 AN: 67658

Other (OTH) AF: 0.520 AC: 1085 AN: 2088

Alfa AF: 0.505 Hom.: 2469

Bravo AF: 0.528

Asia WGS AF: 0.501 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-0.76
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: rs9695310; hg19: chr9-32464135;