rs401671

Variant names:

• chr6-24960419-C-T
• rs401671
• NM_001286446.3:c.76+81432G>A

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+81432G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,166 control chromosomes in the GnomAD database, including 8,241 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 0.32 (8241 hom., cov: 32)
• Consequence: RIPOR2 NM_001286446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286446.3	c.76+81432G>A		intron_variant	Intron 1 of 13		NP_001273375.1
RIPOR2	XM_011515012.2	c.76+81432G>A		intron_variant	Intron 1 of 22		XP_011513314.1
RIPOR2	XM_006715275.3	c.76+81432G>A		intron_variant	Intron 1 of 21		XP_006715338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000510784.8	c.76+81432G>A		intron_variant	Intron 1 of 13	2		ENSP00000441305.1
ENSG00000288887	ENST00000716086.1	n.171+24183C>T		intron_variant	Intron 1 of 5
ENSG00000288887	ENST00000761913.1	n.180-15928C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48125 AN: 152048 Hom.: 8249 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.316 AC: 48119 AN: 152166 Hom.: 8241 Cov.: 32 AF XY: 0.314 AC XY: 23336 AN XY: 74390

African (AFR) AF: 0.197 AC: 8185 AN: 41548

American (AMR) AF: 0.268 AC: 4100 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1492 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1277 AN: 5180

South Asian (SAS) AF: 0.242 AC: 1169 AN: 4826

European-Finnish (FIN) AF: 0.394 AC: 4166 AN: 10572

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26648 AN: 67966

Other (OTH) AF: 0.309 AC: 653 AN: 2112

Alfa AF: 0.373 Hom.: 11944

Bravo AF: 0.301

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.26
PhyloP100		0.85
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: rs401671; hg19: chr6-24960647;