rs75574668

chr6-24840758-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001286445.3(RIPOR2):c.1858-1486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00598 in 1,535,374 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (124 hom., cov: 31)
  • Exomes 𝑓: 0.0042 (99 hom.)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.914

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 6-24840758-G-A is Benign according to our data. Variant chr6-24840758-G-A is described in ClinVar as [Benign]. Clinvar id is 586405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPOR2	NM_001286445.3	c.1858-1486C>T		intron_variant		ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2	c.1858-1486C>T		intron_variant			NM_001286445.3	A2

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3312 AN: 152108 Hom.: 122 Cov.: 31

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00560 AC: 719 AN: 128374 Hom.: 11 AF XY: 0.00509 AC XY: 358 AN XY: 70306

Gnomad AFR exome AF: 0.0697

Gnomad AMR exome AF: 0.00484

Gnomad ASJ exome AF: 0.000124

Gnomad EAS exome AF: 0.000288

Gnomad SAS exome AF: 0.00183

Gnomad FIN exome AF: 0.000557

Gnomad NFE exome AF: 0.00256

Gnomad OTH exome AF: 0.00175

GnomAD4 exome AF: 0.00424 AC: 5869 AN: 1383148 Hom.: 99 Cov.: 31 AF XY: 0.00394 AC XY: 2686 AN XY: 682496

Gnomad4 AFR exome AF: 0.0758

Gnomad4 AMR exome AF: 0.00504

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.000196

Gnomad4 SAS exome AF: 0.00245

Gnomad4 FIN exome AF: 0.000986

Gnomad4 NFE exome AF: 0.00244

Gnomad4 OTH exome AF: 0.00679

GnomAD4 genome AF: 0.0218 AC: 3319 AN: 152226 Hom.: 124 Cov.: 31 AF XY: 0.0203 AC XY: 1514 AN XY: 74432

Gnomad4 AFR AF: 0.0720

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00240

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0110 Hom.: 11

Bravo AF: 0.0246

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 01, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	15
Dann	Benign	0.76

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: rs75574668; hg19: chr6-24840986; COSMIC: COSV52418210; COSMIC: COSV52418210;