chr6-25010771-G-A

Variant names:

• chr6-25010771-G-A
• rs10946741
• NM_001286446.3:c.76+31080C>T

Variant summary

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

The NM_001286446.3(RIPOR2):​c.76+31080C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,896 control chromosomes in the GnomAD database, including 20,180 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 0.51 (20180 hom., cov: 31)
• Consequence: RIPOR2 NM_001286446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 1 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

ENSG00000288887 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPOR2	NM_001286446.3		c.76+31080C>T		intron	N/A	NP_001273375.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPOR2	ENST00000510784.8	TSL:2	c.76+31080C>T		intron	N/A	ENSP00000441305.1
	ENSG00000288887	ENST00000716086.1		n.172-2520G>A		intron	N/A
	ENSG00000288887	ENST00000761916.1		n.99-2520G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76934 AN: 151778 Hom.: 20157 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.507 AC: 77011 AN: 151896 Hom.: 20180 Cov.: 31 AF XY: 0.503 AC XY: 37312 AN XY: 74228

African (AFR) AF: 0.464 AC: 19202 AN: 41404

American (AMR) AF: 0.460 AC: 7021 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1394 AN: 3470

East Asian (EAS) AF: 0.170 AC: 877 AN: 5148

South Asian (SAS) AF: 0.447 AC: 2155 AN: 4818

European-Finnish (FIN) AF: 0.593 AC: 6245 AN: 10538

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38268 AN: 67932

Other (OTH) AF: 0.466 AC: 981 AN: 2106

Alfa AF: 0.524 Hom.: 37647

Bravo AF: 0.491

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.84
PhyloP100		0.056
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: rs10946741; hg19: chr6-25010999;