9-32526235-G-C

Variant names:

• chr9-32526235-G-C
• rs3739674
• ENST00000681750.1:c.-45+24539C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000681750.1(ENSG00000288684):​c.-45+24539C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,290,604 control chromosomes in the GnomAD database, including 237,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (24720 hom., cov: 29)
  • Exomes 𝑓: 0.61 (212310 hom.)
• Consequence: ENSG00000288684 ENST00000681750.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.157
• Publications: 17 publications found

Genes affected

ENSG00000288684 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-32526235-G-C is Benign according to our data. Variant chr9-32526235-G-C is described in ClinVar as Benign. ClinVar VariationId is 2637878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIGI	NM_014314.4	c.-69C>G		upstream_gene_variant		ENST00000379883.3	NP_055129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288684	ENST00000681750.1	c.-45+24539C>G		intron_variant	Intron 3 of 19			ENSP00000506413.1
RIGI	ENST00000379883.3	c.-69C>G		upstream_gene_variant		1	NM_014314.4	ENSP00000369213.2

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85988 AN: 151554 Hom.: 24706 Cov.: 29

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.608 AC: 692262 AN: 1138932 Hom.: 212310 Cov.: 14 AF XY: 0.611 AC XY: 350457 AN XY: 574020

African (AFR) AF: 0.486 AC: 12459 AN: 25638

American (AMR) AF: 0.466 AC: 14685 AN: 31486

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 14390 AN: 22102

East Asian (EAS) AF: 0.389 AC: 13626 AN: 35056

South Asian (SAS) AF: 0.637 AC: 48412 AN: 75964

European-Finnish (FIN) AF: 0.532 AC: 21681 AN: 40742

Middle Eastern (MID) AF: 0.668 AC: 2579 AN: 3860

European-Non Finnish (NFE) AF: 0.626 AC: 535031 AN: 854938

Other (OTH) AF: 0.598 AC: 29399 AN: 49146

GnomAD4 genome AF: 0.567 AC: 86027 AN: 151672 Hom.: 24720 Cov.: 29 AF XY: 0.563 AC XY: 41740 AN XY: 74086

African (AFR) AF: 0.497 AC: 20526 AN: 41338

American (AMR) AF: 0.510 AC: 7773 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2214 AN: 3466

East Asian (EAS) AF: 0.413 AC: 2114 AN: 5116

South Asian (SAS) AF: 0.640 AC: 3063 AN: 4788

European-Finnish (FIN) AF: 0.516 AC: 5413 AN: 10486

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42944 AN: 67934

Other (OTH) AF: 0.578 AC: 1212 AN: 2098

Alfa AF: 0.604 Hom.: 3475

Bravo AF: 0.560

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 44% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.72
PhyloP100		-0.16
PromoterAI		-0.081	Neutral
Mutation Taster		=300/0	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: rs3739674; hg19: chr9-32526233; COSMIC: COSV65884177; COSMIC: COSV65884177;