rs74477879

Variant names:

Variant summary

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

The NM_014722.5(RIPOR2):c.1146C>G(p.Phe382Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 1,551,674 control chromosomes in the GnomAD database, including 220 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 125 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 95 hom. )

Consequence

RIPOR2
NM_014722.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.74

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 (MetaRNN=0.0014749169).

BP6

Variant 6-24847623-G-C is Benign according to our data. Variant chr6-24847623-G-C is described in ClinVar as [Benign]. Clinvar id is 509125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3 link	c.1164+402C>G		intron_variant	Intron 12 of 21	ENST00000643898.2	NP_001273374.1	A0A2R8YEE0B7Z5J9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2 link	c.1164+402C>G		intron_variant	Intron 12 of 21		NM_001286445.3	ENSP00000494268.2		A0A2R8YEE0

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3254

AN:

152196

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0718

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00195

Gnomad OTH

AF:

0.0162

GnomAD3 exomes

AF:

0.00515

AC:

805

AN:

156436

Hom.:

AF XY:

0.00438

AC XY:

363

AN XY:

82874

show subpopulations

Gnomad AFR exome

AF:

0.0705

Gnomad AMR exome

AF:

0.00482

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.000179

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00356

AC:

4980

AN:

1399360

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

2223

AN XY:

690188

show subpopulations

Gnomad4 AFR exome

AF:

0.0756

Gnomad4 AMR exome

AF:

0.00504

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.000568

Gnomad4 NFE exome

AF:

0.00185

Gnomad4 OTH exome

AF:

0.00586

GnomAD4 genome

AF:

0.0214

AC:

3261

AN:

152314

Hom.:

125

Cov.:

AF XY:

0.0198

AC XY:

1477

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0718

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00196

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00464

Hom.:

Bravo

AF:

0.0244

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00156

AC:

ExAC

AF:

0.00724

AC:

188

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 24, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Oct 23, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.00069

T;T;T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.53

.;T;.;T

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.040

.;.;N;.

REVEL

Benign

0.035

Sift

Benign

0.70

.;.;T;.

Sift4G

Benign

0.70

.;T;T;.

Polyphen

0.0

B;B;B;.

Vest4

0.081, 0.069

MutPred

0.31

Loss of solvent accessibility (P = 0.001);Loss of solvent accessibility (P = 0.001);Loss of solvent accessibility (P = 0.001);Loss of solvent accessibility (P = 0.001);

MVP

0.10

MPC

0.35

ClinPred

0.0087

GERP RS

4.3

Varity_R

0.089

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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