6-24806485-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001286445.3(RIPOR2):c.3044-12T>C variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008783

Clinical Significance

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

Conservation

PhyloP100: 1.94

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 -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 GnomAd at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPOR2	NM_001286445.3 linkuse as main transcript	c.3044-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2 linkuse as main transcript	c.3044-12T>C	splice_polypyrimidine_tract_variant, intron_variant		NM_001286445.3	A2
RIPOR2	ENST00000259698.9 linkuse as main transcript	c.3107-12T>C	splice_polypyrimidine_tract_variant, intron_variant	1		A2	Q9Y4F9-1
RIPOR2	ENST00000538035.6 linkuse as main transcript	c.2957-12T>C	splice_polypyrimidine_tract_variant, intron_variant	2		A2
RIPOR2	ENST00000613507.4 linkuse as main transcript	c.3107-12T>C	splice_polypyrimidine_tract_variant, intron_variant	5		A2	Q9Y4F9-1

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

GnomAD3 exomes

AF:

0.00559

AC:

772

AN:

138184

Hom.:

AF XY:

0.00568

AC XY:

416

AN XY:

73192

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 SAS exome

AF:

0.00214

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

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.00333

Gnomad4 EAS exome

AF:

0.0000567

Gnomad4 SAS exome

AF:

0.00193

Gnomad4 FIN exome

AF:

0.00913

Gnomad4 NFE exome

AF:

0.00886

Gnomad4 OTH exome

AF:

0.00660

GnomAD4 genome

AF:

0.00598

AC:

894

AN:

149510

Hom.:

Cov.:

AF XY:

0.00558

AC XY:

407

AN XY:

72884

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00427

Gnomad4 ASJ

AF:

0.00407

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00107

Gnomad4 FIN

AF:

0.00758

Gnomad4 NFE

AF:

0.00882

Gnomad4 OTH

AF:

0.00393

Alfa

AF:

0.00657

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

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 24, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

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

Dann

Benign

0.47

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

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