rs10484893

Variant names:

• chr6-24888323-C-T
• rs10484893
• NM_001286445.3:c.62-12506G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286445.3(RIPOR2):​c.62-12506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,182 control chromosomes in the GnomAD database, including 1,171 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 0.12 (1171 hom., cov: 32)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 3 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.62-12506G>A		intron_variant	Intron 1 of 21	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.62-12506G>A		intron_variant	Intron 1 of 21		NM_001286445.3	ENSP00000494268.2

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17824 AN: 152064 Hom.: 1171 Cov.: 32

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.0992

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0727

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.117 AC: 17825 AN: 152182 Hom.: 1171 Cov.: 32 AF XY: 0.117 AC XY: 8712 AN XY: 74384

African (AFR) AF: 0.0634 AC: 2632 AN: 41544

American (AMR) AF: 0.0989 AC: 1511 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3472

East Asian (EAS) AF: 0.0727 AC: 377 AN: 5184

South Asian (SAS) AF: 0.163 AC: 785 AN: 4824

European-Finnish (FIN) AF: 0.141 AC: 1491 AN: 10564

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10066 AN: 68004

Other (OTH) AF: 0.108 AC: 228 AN: 2110

Alfa AF: 0.141 Hom.: 865

Bravo AF: 0.109

Asia WGS AF: 0.119 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		-0.16
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: rs10484893; hg19: chr6-24888551;