rs401671

chr6-24960419-C-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+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

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=-0.91).
• 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/exons	MANE	UniProt
RIPOR2	NM_001286446.3	c.76+81432G>A		intron_variant
RIPOR2	XM_006715275.3	c.76+81432G>A		intron_variant
RIPOR2	XM_006715281.4	c.76+81432G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000510784.8	c.76+81432G>A		intron_variant		2		P2

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

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.309

Alfa AF: 0.372 Hom.: 8332

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs401671; hg19: chr6-24960647;