6-24806549-T-A

Position:

• chr6-24806549-T-A

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.3044-76A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,084,600 control chromosomes in the GnomAD database, including 137,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16104 hom., cov: 32)
  • Exomes 𝑓: 0.50 (121151 hom.)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.34

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]

ENSG00000282804 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 6-24806549-T-A is Benign according to our data. Variant chr6-24806549-T-A is described in ClinVar as [Benign]. Clinvar id is 1265462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.3044-76A>T		intron_variant		ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.3044-76A>T		intron_variant			NM_001286445.3	ENSP00000494268.2
ENSG00000282804	ENST00000562221.1	c.83-76A>T		intron_variant		5		ENSP00000455145.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67890 AN: 151880 Hom.: 16104 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.502 AC: 468214 AN: 932602 Hom.: 121151 AF XY: 0.501 AC XY: 235298 AN XY: 469814

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.447 AC: 67926 AN: 151998 Hom.: 16104 Cov.: 32 AF XY: 0.446 AC XY: 33109 AN XY: 74266

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.421

Alfa AF: 0.353 Hom.: 993

Bravo AF: 0.433

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

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.42

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: rs9379689; hg19: chr6-24806777; COSMIC: COSV52418575;