chr6-24848144-C-T

Position:

chr6-24848144-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001286445.3(RIPOR2):c.1045G>A(p.Val349Met) variant causes a missense change. The variant allele was found at a frequency of 0.00901 in 1,613,324 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 117 hom. )

Consequence

RIPOR2
NM_001286445.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.74

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=0.0045339167).

BP6

Variant 6-24848144-C-T is Benign according to our data. Variant chr6-24848144-C-T is described in ClinVar as [Benign]. Clinvar id is 508603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-24848144-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00925 (1409/152280) while in subpopulation AMR AF= 0.0347 (531/15286). AF 95% confidence interval is 0.0323. There are 13 homozygotes in gnomad4. There are 727 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR2	NM_001286445.3 link	c.1045G>A	p.Val349Met	missense_variant	12/22	ENST00000643898.2	NP_001273374.1	A0A2R8YEE0B7Z5J9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2 link	c.1045G>A	p.Val349Met	missense_variant	12/22		NM_001286445.3	ENSP00000494268.2		A0A2R8YEE0

Frequencies

GnomAD3 genomes

AF:

0.00925

AC:

1408

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0348

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0165

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00683

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.0131

AC:

3242

AN:

247722

Hom.:

AF XY:

0.0113

AC XY:

1524

AN XY:

134434

show subpopulations

Gnomad AFR exome

AF:

0.00151

Gnomad AMR exome

AF:

0.0464

Gnomad ASJ exome

AF:

0.000600

Gnomad EAS exome

AF:

0.0178

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.00677

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.00899

AC:

13134

AN:

1461044

Hom.:

117

Cov.:

AF XY:

0.00872

AC XY:

6337

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.0434

Gnomad4 ASJ exome

AF:

0.000958

Gnomad4 EAS exome

AF:

0.0177

Gnomad4 SAS exome

AF:

0.00430

Gnomad4 FIN exome

AF:

0.0150

Gnomad4 NFE exome

AF:

0.00797

Gnomad4 OTH exome

AF:

0.00633

GnomAD4 genome

AF:

0.00925

AC:

1409

AN:

152280

Hom.:

Cov.:

AF XY:

0.00976

AC XY:

727

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.0347

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0166

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.0200

Gnomad4 NFE

AF:

0.00684

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00806

Hom.:

Bravo

AF:

0.0104

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000755

AC:

ESP6500EA

AF:

0.00742

AC:

ExAC

AF:

0.0110

AC:

1326

Asia WGS

AF:

0.00808

AC:

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	Oct 25, 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	p.Val320Met in exon 12 of FAM65B: This variant is not expected to have clinical significance because it has been identified in 5.24% (567/10816) of Latino chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs35331811). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2025	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;T;T;.;.;.;T;.;.;.;.;.;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

.;D;.;D;D;.;D;D;.;D;D;.;D

MetaRNN

Benign

0.0045

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.18

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.65

.;.;N;.;.;N;N;N;.;.;.;.;.

REVEL

Benign

0.29

Sift

Benign

0.042

.;.;D;.;.;D;D;D;.;.;.;.;.

Sift4G

Benign

0.097

.;T;T;.;.;T;T;T;.;.;.;.;.

Polyphen

1.0

D;D;D;.;.;D;D;.;D;D;.;.;.

Vest4

0.34, 0.38, 0.54, 0.55, 0.56

MPC

0.99

ClinPred

0.011

GERP RS

5.5

Varity_R

0.070

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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