6-24806511-C-CTT

Variant names:

• chr6-24806511-C-CTT
• rs5875006
• NM_001286445.3:c.3044-39_3044-38insAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001286445.3(RIPOR2):​c.3044-39_3044-38insAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16018 hom., cov: 0)
  • Exomes 𝑓: 0.51 (170381 hom.)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.404
• Publications: 5 publications found

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

ENSG00000282804 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-24806511-C-CTT is Benign according to our data. Variant chr6-24806511-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1285903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.3044-39_3044-38insAA		intron_variant	Intron 21 of 21	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.3044-39_3044-38insAA		intron_variant	Intron 21 of 21		NM_001286445.3	ENSP00000494268.2
ENSG00000282804	ENST00000562221.1	c.83-39_83-38insAA		intron_variant	Intron 1 of 2	5		ENSP00000455145.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67735 AN: 151750 Hom.: 16018 Cov.: 0

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.427

GnomAD2 exomes AF: 0.466 AC: 65286 AN: 140066 AF XY: 0.470

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.532

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.519

Gnomad NFE exome AF: 0.538

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.511 AC: 648217 AN: 1269314 Hom.: 170381 Cov.: 17 AF XY: 0.510 AC XY: 321259 AN XY: 630188

African (AFR) AF: 0.298 AC: 8402 AN: 28214

American (AMR) AF: 0.419 AC: 13076 AN: 31192

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 12712 AN: 24022

East Asian (EAS) AF: 0.215 AC: 7362 AN: 34232

South Asian (SAS) AF: 0.431 AC: 31851 AN: 73860

European-Finnish (FIN) AF: 0.519 AC: 25156 AN: 48438

Middle Eastern (MID) AF: 0.516 AC: 2796 AN: 5422

European-Non Finnish (NFE) AF: 0.537 AC: 521351 AN: 970342

Other (OTH) AF: 0.476 AC: 25511 AN: 53592

GnomAD4 genome AF: 0.446 AC: 67770 AN: 151862 Hom.: 16018 Cov.: 0 AF XY: 0.445 AC XY: 33021 AN XY: 74194

African (AFR) AF: 0.310 AC: 12869 AN: 41448

American (AMR) AF: 0.441 AC: 6735 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1841 AN: 3462

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5176

South Asian (SAS) AF: 0.420 AC: 2024 AN: 4824

European-Finnish (FIN) AF: 0.520 AC: 5460 AN: 10502

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36324 AN: 67876

Other (OTH) AF: 0.422 AC: 891 AN: 2110

Alfa AF: 0.414 Hom.: 1869

Bravo AF: 0.433

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5875006; hg19: chr6-24806739;