rs10484892

Variant names:

• chr6-24893550-G-A
• rs10484892
• NM_001286445.3:c.62-17733C>T

Variant summary

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

The NM_001286445.3(RIPOR2):​c.62-17733C>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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.62-17733C>T		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.62-17733C>T		intron_variant	Intron 1 of 21		NM_001286445.3	ENSP00000494268.2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16603 AN: 152090 Hom.: 1020 Cov.: 32

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.: 32 AF XY: 0.109 AC XY: 8140 AN XY: 74412

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: 20 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9396 AN: 68010

Other (OTH) AF: 0.0966 AC: 204 AN: 2112

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.57
PhyloP100		0.27
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: rs10484892; hg19: chr6-24893778;