rs10946741

Positions:

• chr6-25010771-G-A
• chr6-25010771-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR2	NM_001286446.3	c.76+31080C>T		intron_variant			NP_001273375.1
RIPOR2	XM_006715275.3	c.76+31080C>T		intron_variant			XP_006715338.1
RIPOR2	XM_006715281.4	c.76+31080C>T		intron_variant			XP_006715344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000510784.8	c.76+31080C>T		intron_variant		2		ENSP00000441305	P2

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

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.466

Alfa AF: 0.530 Hom.: 23887

Bravo AF: 0.491

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10946741; hg19: chr6-25010999;