6-24806110-T-C

Variant names:

• chr6-24806110-T-C
• rs9393586
• NM_001286445.3:c.*263A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001286445.3(RIPOR2):​c.*263A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 413,228 control chromosomes in the GnomAD database, including 46,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16018 hom., cov: 30)
  • Exomes 𝑓: 0.47 (30789 hom.)
• Consequence: RIPOR2 NM_001286445.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.44
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP6: Variant 6-24806110-T-C is Benign according to our data. Variant chr6-24806110-T-C is described in ClinVar as [Benign]. Clinvar id is 1249750.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.*263A>G		3_prime_UTR_variant	Exon 22 of 22	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.*263A>G		3_prime_UTR_variant	Exon 22 of 22		NM_001286445.3	ENSP00000494268.2
ENSG00000282804	ENST00000562221.1	c.*6+257A>G		intron_variant	Intron 2 of 2	5		ENSP00000455145.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67671 AN: 151766 Hom.: 16018 Cov.: 30

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.473 AC: 123697 AN: 261344 Hom.: 30789 Cov.: 0 AF XY: 0.470 AC XY: 64571 AN XY: 137268

African (AFR) AF: 0.282 AC: 1784 AN: 6316

American (AMR) AF: 0.417 AC: 2632 AN: 6312

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 4496 AN: 8696

East Asian (EAS) AF: 0.208 AC: 3159 AN: 15190

South Asian (SAS) AF: 0.409 AC: 11264 AN: 27518

European-Finnish (FIN) AF: 0.490 AC: 8005 AN: 16340

Middle Eastern (MID) AF: 0.475 AC: 577 AN: 1216

European-Non Finnish (NFE) AF: 0.515 AC: 84462 AN: 163884

Other (OTH) AF: 0.461 AC: 7318 AN: 15872

GnomAD4 genome AF: 0.446 AC: 67707 AN: 151884 Hom.: 16018 Cov.: 30 AF XY: 0.445 AC XY: 33020 AN XY: 74196

African (AFR) AF: 0.311 AC: 12865 AN: 41414

American (AMR) AF: 0.441 AC: 6732 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1846 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1021 AN: 5168

South Asian (SAS) AF: 0.420 AC: 2016 AN: 4804

European-Finnish (FIN) AF: 0.520 AC: 5487 AN: 10546

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.534 AC: 36261 AN: 67920

Other (OTH) AF: 0.420 AC: 885 AN: 2106

Alfa AF: 0.371 Hom.: 1092

Bravo AF: 0.432

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

Nov 11, 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
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.13
DANN	Benign	0.11
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9393586; hg19: chr6-24806338;