6-24806110-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001286445.3(RIPOR2):c.*263A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 413,228 control chromosomes in the GnomAD database, including 46,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16018 hom., cov: 30)
  • Exomes 𝑓: 0.47 (30789 hom.)
• Consequence: RIPOR2 NM_001286445.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.44

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP6: Variant 6-24806110-T-C is Benign according to our data. Variant chr6-24806110-T-C is described in ClinVar as [Benign]. Clinvar id is 1249750.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPOR2	NM_001286445.3	c.*263A>G		3_prime_UTR_variant	22/22	ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2	c.*263A>G		3_prime_UTR_variant	22/22		NM_001286445.3	A2
RIPOR2	ENST00000259698.9	c.*263A>G		3_prime_UTR_variant	23/23	1		A2
RIPOR2	ENST00000538035.6	c.*263A>G		3_prime_UTR_variant	22/22	2		A2
RIPOR2	ENST00000613507.4	c.*263A>G		3_prime_UTR_variant	23/23	5		A2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67671 AN: 151766 Hom.: 16018 Cov.: 30

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.473 AC: 123697 AN: 261344 Hom.: 30789 Cov.: 0 AF XY: 0.470 AC XY: 64571 AN XY: 137268

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.461

GnomAD4 genome AF: 0.446 AC: 67707 AN: 151884 Hom.: 16018 Cov.: 30 AF XY: 0.445 AC XY: 33020 AN XY: 74196

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.420

Alfa AF: 0.371 Hom.: 1092

Bravo AF: 0.432

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.13
Dann	Benign	0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs9393586; hg19: chr6-24806338;