Genetic Variant RIGI:c.107-3357A>G (chr9-32504296-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.90

Publications

6 publications found

Variant links:

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), G2P, Ambry Genetics
Singleton-Merten dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RIGI links:

ENSG00000288684 (HGNC:):

ENSG00000288684 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIGI	NM_014314.4	MANE Select	c.107-3357A>G	intron	N/A	NP_055129.2
RIGI	NM_001385907.1		c.107-3357A>G	intron	N/A	NP_001372836.1	A0AAQ5BIG4
RIGI	NM_001385913.1		c.107-3357A>G	intron	N/A	NP_001372842.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIGI	ENST00000379883.3	TSL:1 MANE Select	c.107-3357A>G	intron	N/A	ENSP00000369213.2	O95786-1
ENSG00000288684	ENST00000681750.1		c.-44-3357A>G	intron	N/A	ENSP00000506413.1	A0A7P0TB70
RIGI	ENST00000715271.1		c.107-3360A>G	intron	N/A	ENSP00000520440.1	A0AAQ5BIF4

Frequencies

GnomAD3 genomes

AF:

0.602

AC:

91318

AN:

151702

Hom.:

27881

Cov.:

show subpopulations

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.:

AF XY:

0.594

AC XY:

44099

AN XY:

74192

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1798

3597

5395

7194

8992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.618

Hom.:

13693

Bravo

AF:

0.599

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.043

(source)

DANN

Benign

0.22

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over