NM_001286445.3:c.3044-12T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001286445.3(RIPOR2):c.3044-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00753 in 1,522,738 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 49 hom. )

Consequence

RIPOR2
NM_001286445.3 intron

Scores

Splicing: ADA: 0.00008783

Clinical Significance

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

Conservation

PhyloP100: 1.94

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 104
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal dominant nonsyndromic hearing loss 21
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

RIPOR2 links:

ENSG00000282804 (HGNC:):

ENSG00000282804 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-24806485-A-G is Benign according to our data. Variant chr6-24806485-A-G is described in ClinVar as [Benign]. Clinvar id is 517552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3 link	c.3044-12T>C		intron_variant	Intron 21 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.3044-12T>C		intron_variant	Intron 21 of 21		NM_001286445.3	ENSP00000494268.2		A0A2R8YEE0
ENSG00000282804	ENST00000562221.1 link	c.83-12T>C		intron_variant	Intron 1 of 2	5		ENSP00000455145.1		H3BP45

Frequencies

GnomAD3 genomes

AF:

0.00599

AC:

895

AN:

149392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00144

Gnomad AMI

AF:

0.0856

Gnomad AMR

AF:

0.00428

Gnomad ASJ

AF:

0.00407

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.00758

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00884

Gnomad OTH

AF:

0.00398

GnomAD2 exomes

AF:

0.00559

AC:

772

AN:

138184

AF XY:

0.00568

show subpopulations

Gnomad AFR exome

AF:

0.00192

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00292

Gnomad EAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.00682

Gnomad NFE exome

AF:

0.00958

Gnomad OTH exome

AF:

0.00394

GnomAD4 exome

AF:

0.00770

AC:

10571

AN:

1373228

Hom.:

Cov.:

AF XY:

0.00738

AC XY:

5009

AN XY:

678280

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

30720

American (AMR)

AF:

0.00215

AC:

AN:

33560

Ashkenazi Jewish (ASJ)

AF:

0.00333

AC:

AN:

24926

East Asian (EAS)

AF:

0.0000567

AC:

AN:

35278

South Asian (SAS)

AF:

0.00193

AC:

149

AN:

77302

European-Finnish (FIN)

AF:

0.00913

AC:

450

AN:

49264

Middle Eastern (MID)

AF:

0.00265

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00886

AC:

9389

AN:

1059364

Other (OTH)

AF:

0.00660

AC:

377

AN:

57164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

506

1012

1518

2024

2530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00598

AC:

894

AN:

149510

Hom.:

Cov.:

AF XY:

0.00558

AC XY:

407

AN XY:

72884

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41006

American (AMR)

AF:

0.00427

AC:

AN:

14742

Ashkenazi Jewish (ASJ)

AF:

0.00407

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00107

AC:

AN:

4674

European-Finnish (FIN)

AF:

0.00758

AC:

AN:

10158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00882

AC:

592

AN:

67100

Other (OTH)

AF:

0.00393

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

117

156

195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00664

Hom.:

Bravo

AF:

0.00584

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.3107-12T>C in intron 22 of FAM65B: This variant is not expected to have clinic al significance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.82% (76/9312) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs115680381). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.6

(source)

DANN

Benign

0.47

PhyloP100

1.9

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.014

SpliceAI score (max)

0.14

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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NM_001286445.3:c.3044-12T>C

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