chr9-32459452-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014314.4(RIGI):c.2400A>C(p.Val800Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,612,956 control chromosomes in the GnomAD database, including 98,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8359 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90417 hom. )

Consequence

RIGI
NM_014314.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.132

Publications

34 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), Ambry Genetics, G2P
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 9-32459452-T-G is Benign according to our data. Variant chr9-32459452-T-G is described in ClinVar as [Benign]. Clinvar id is 1169347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.132 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIGI	NM_014314.4 link	c.2400A>C	p.Val800Val	synonymous_variant	Exon 17 of 18	ENST00000379883.3	NP_055129.2	O95786-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIGI	ENST00000379883.3 link	c.2400A>C	p.Val800Val	synonymous_variant	Exon 17 of 18	1	NM_014314.4	ENSP00000369213.2		O95786-1
ENSG00000288684	ENST00000681750.1 link	c.2250A>C	p.Val750Val	synonymous_variant	Exon 19 of 20			ENSP00000506413.1		A0A7P0TB70

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49411

AN:

151928

Hom.:

8345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.362

GnomAD2 exomes

AF:

0.346

AC:

86766

AN:

250680

AF XY:

0.343

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.393

Gnomad EAS exome

AF:

0.494

Gnomad FIN exome

AF:

0.328

Gnomad NFE exome

AF:

0.365

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.349

AC:

510361

AN:

1460910

Hom.:

90417

Cov.:

AF XY:

0.347

AC XY:

252268

AN XY:

726784

show subpopulations

African (AFR)

AF:

0.228

AC:

7599

AN:

33390

American (AMR)

AF:

0.342

AC:

15249

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

10407

AN:

26116

East Asian (EAS)

AF:

0.440

AC:

17467

AN:

39668

South Asian (SAS)

AF:

0.253

AC:

21840

AN:

86162

European-Finnish (FIN)

AF:

0.330

AC:

17602

AN:

53280

Middle Eastern (MID)

AF:

0.382

AC:

2201

AN:

5766

European-Non Finnish (NFE)

AF:

0.357

AC:

396895

AN:

1111650

Other (OTH)

AF:

0.350

AC:

21101

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

16505

33010

49515

66020

82525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12592

25184

37776

50368

62960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.325

AC:

49439

AN:

152046

Hom.:

8359

Cov.:

AF XY:

0.324

AC XY:

24091

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.237

AC:

9829

AN:

41484

American (AMR)

AF:

0.354

AC:

5410

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

1338

AN:

3472

East Asian (EAS)

AF:

0.473

AC:

2435

AN:

5150

South Asian (SAS)

AF:

0.255

AC:

1226

AN:

4814

European-Finnish (FIN)

AF:

0.317

AC:

3351

AN:

10566

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.362

AC:

24622

AN:

67968

Other (OTH)

AF:

0.368

AC:

777

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1661

3322

4983

6644

8305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.354

Hom.:

24030

Bravo

AF:

0.327

Asia WGS

AF:

0.372

AC:

1293

AN:

3478

EpiCase

AF:

0.366

EpiControl

AF:

0.371

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 14, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 52% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -

Singleton-Merten syndrome 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.8

(source)

DANN

Benign

0.57

PhyloP100

-0.13

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over