rs9379693

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001286445.3(RIPOR2):c.3043+9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,517,870 control chromosomes in the GnomAD database, including 15,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1314 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14156 hom. )

Consequence

RIPOR2
NM_001286445.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.338

Variant links:

Genes affected

RIPOR2 (HGNC:13872): (RHO family interacting cell polarization regulator 2) This gene encodes an atypical inhibitor of the small G protein RhoA. Inhibition of RhoA activity by the encoded protein mediates myoblast fusion and polarization of T cells and neutrophils. The encoded protein is a component of hair cell stereocilia that is essential for hearing. A splice site mutation in this gene results in hearing loss in human patients. [provided by RefSeq, Sep 2016]

RIPOR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 6-24809708-A-T is Benign according to our data. Variant chr6-24809708-A-T is described in ClinVar as [Benign]. Clinvar id is 517553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPOR2	NM_001286445.3 linkuse as main transcript	c.3043+9T>A		intron_variant		ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2 linkuse as main transcript	c.3043+9T>A	intron_variant		NM_001286445.3	A2
RIPOR2	ENST00000259698.9 linkuse as main transcript	c.3106+9T>A	intron_variant	1		A2	Q9Y4F9-1
RIPOR2	ENST00000538035.6 linkuse as main transcript	c.2956+9T>A	intron_variant	2		A2
RIPOR2	ENST00000613507.4 linkuse as main transcript	c.3106+9T>A	intron_variant	5		A2	Q9Y4F9-1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18902

AN:

152104

Hom.:

1312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0775

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.140

AC:

21907

AN:

156336

Hom.:

1639

AF XY:

0.139

AC XY:

11508

AN XY:

82862

show subpopulations

Gnomad AFR exome

AF:

0.0746

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.142

AC:

193750

AN:

1365652

Hom.:

14156

Cov.:

AF XY:

0.141

AC XY:

95378

AN XY:

675634

show subpopulations

Gnomad4 AFR exome

AF:

0.0714

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.124

AC:

18911

AN:

152218

Hom.:

1314

Cov.:

AF XY:

0.125

AC XY:

9303

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0773

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.140

Hom.:

539

Bravo

AF:

0.124

Asia WGS

AF:

0.0890

AC:

310

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	c.3106+9T>A in intron 22 of FAM65B: This variant is not expected to have clinica l significance because it does not alter an amino acid residue, is not located w ithin the splice consensus sequence, and has been identified in 15.70% (255/1624 ) of Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs9379693). -

Autosomal recessive nonsyndromic hearing loss 104

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

Cadd

Benign

9.7

Dann

Benign

0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over