6-24818557-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001286445.3(RIPOR2):​c.2937T>C​(p.Ala979Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,547,186 control chromosomes in the GnomAD database, including 89,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8023 hom., cov: 30)
Exomes 𝑓: 0.33 ( 81318 hom. )

Consequence

RIPOR2
NM_001286445.3 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.0730
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 6-24818557-A-G is Benign according to our data. Variant chr6-24818557-A-G is described in ClinVar as [Benign]. Clinvar id is 508096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.073 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RIPOR2NM_001286445.3 linkc.2937T>C p.Ala979Ala synonymous_variant Exon 20 of 22 ENST00000643898.2 NP_001273374.1 A0A2R8YEE0B7Z5J9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RIPOR2ENST00000643898.2 linkc.2937T>C p.Ala979Ala synonymous_variant Exon 20 of 22 NM_001286445.3 ENSP00000494268.2 A0A2R8YEE0
RIPOR2ENST00000259698.9 linkc.3000T>C p.Ala1000Ala synonymous_variant Exon 21 of 23 1 ENSP00000259698.4 Q9Y4F9-1
RIPOR2ENST00000613507.4 linkc.3000T>C p.Ala1000Ala synonymous_variant Exon 21 of 23 5 ENSP00000482957.1 Q9Y4F9-1
RIPOR2ENST00000538035.6 linkc.2850T>C p.Ala950Ala synonymous_variant Exon 20 of 22 2 ENSP00000441138.2 F5GX51

Frequencies

GnomAD3 genomes
AF:
0.306
AC:
46460
AN:
151866
Hom.:
8017
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.187
Gnomad AMI
AF:
0.485
Gnomad AMR
AF:
0.375
Gnomad ASJ
AF:
0.254
Gnomad EAS
AF:
0.684
Gnomad SAS
AF:
0.458
Gnomad FIN
AF:
0.392
Gnomad MID
AF:
0.228
Gnomad NFE
AF:
0.311
Gnomad OTH
AF:
0.310
GnomAD3 exomes
AF:
0.378
AC:
59163
AN:
156506
Hom.:
12350
AF XY:
0.379
AC XY:
31371
AN XY:
82800
show subpopulations
Gnomad AFR exome
AF:
0.188
Gnomad AMR exome
AF:
0.455
Gnomad ASJ exome
AF:
0.260
Gnomad EAS exome
AF:
0.686
Gnomad SAS exome
AF:
0.446
Gnomad FIN exome
AF:
0.395
Gnomad NFE exome
AF:
0.306
Gnomad OTH exome
AF:
0.338
GnomAD4 exome
AF:
0.332
AC:
463697
AN:
1395202
Hom.:
81318
Cov.:
31
AF XY:
0.336
AC XY:
231096
AN XY:
688286
show subpopulations
Gnomad4 AFR exome
AF:
0.179
Gnomad4 AMR exome
AF:
0.440
Gnomad4 ASJ exome
AF:
0.261
Gnomad4 EAS exome
AF:
0.664
Gnomad4 SAS exome
AF:
0.448
Gnomad4 FIN exome
AF:
0.396
Gnomad4 NFE exome
AF:
0.313
Gnomad4 OTH exome
AF:
0.337
GnomAD4 genome
AF:
0.306
AC:
46500
AN:
151984
Hom.:
8023
Cov.:
30
AF XY:
0.315
AC XY:
23385
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.187
Gnomad4 AMR
AF:
0.375
Gnomad4 ASJ
AF:
0.254
Gnomad4 EAS
AF:
0.683
Gnomad4 SAS
AF:
0.459
Gnomad4 FIN
AF:
0.392
Gnomad4 NFE
AF:
0.311
Gnomad4 OTH
AF:
0.314
Alfa
AF:
0.293
Hom.:
2916
Bravo
AF:
0.300
Asia WGS
AF:
0.542
AC:
1881
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Aug 23, 2017
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

p.Ala1000Ala in exon 21 of FAM65B: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wi thin the splice consensus sequence, and has been identified in 67.95% (424/624) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs9358802). -

May 09, 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. -

not provided Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
7.8
DANN
Benign
0.59

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9358802; hg19: chr6-24818785; COSMIC: COSV52418661; API