Genetic Variant NM_001286445.3:c.62-17733C>T (chr6-24893550-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001286445.3(RIPOR2):c.62-17733C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,208 control chromosomes in the GnomAD database, including 1,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1021 hom., cov: 32)

Consequence

RIPOR2
NM_001286445.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.267

Publications

2 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):

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

RIPOR2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001286445.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286445.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIPOR2	NM_001286445.3	MANE Select	c.62-17733C>T	intron	N/A	NP_001273374.1	A0A2R8YEE0
RIPOR2	NM_014722.5		c.-27+17268C>T	intron	N/A	NP_055537.2
RIPOR2	NM_001346031.2		c.-27+17268C>T	intron	N/A	NP_001332960.1	F5GX51

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIPOR2	ENST00000643898.2	MANE Select	c.62-17733C>T	intron	N/A	ENSP00000494268.2	A0A2R8YEE0
RIPOR2	ENST00000259698.9	TSL:1	c.-27+17268C>T	intron	N/A	ENSP00000259698.4	Q9Y4F9-1
RIPOR2	ENST00000613507.4	TSL:5	c.-26-17733C>T	intron	N/A	ENSP00000482957.1	Q9Y4F9-1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16603

AN:

152090

Hom.:

1020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0613

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.0878

Gnomad ASJ

AF:

0.0856

Gnomad EAS

AF:

0.0729

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.0976

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.109

AC:

16608

AN:

152208

Hom.:

1021

Cov.:

AF XY:

0.109

AC XY:

8140

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0613

AC:

2546

AN:

41524

American (AMR)

AF:

0.0875

AC:

1338

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0856

AC:

297

AN:

3468

East Asian (EAS)

AF:

0.0729

AC:

378

AN:

5184

South Asian (SAS)

AF:

0.160

AC:

770

AN:

4824

European-Finnish (FIN)

AF:

0.140

AC:

1486

AN:

10592

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9396

AN:

68010

Other (OTH)

AF:

0.0966

AC:

204

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

747

1494

2242

2989

3736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.131

Hom.:

875

Bravo

AF:

0.100

Asia WGS

AF:

0.118

AC:

409

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over