6-24809646-A-C

Position:

• chr6-24809646-A-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.3043+71T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,021,250 control chromosomes in the GnomAD database, including 59,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8101 hom., cov: 31)
  • Exomes 𝑓: 0.34 (51330 hom.)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.320

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=-0.83).
• BP6: Variant 6-24809646-A-C is Benign according to our data. Variant chr6-24809646-A-C is described in ClinVar as [Benign]. Clinvar id is 1228095.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPOR2	NM_001286445.3	c.3043+71T>G		intron_variant		ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2	c.3043+71T>G		intron_variant			NM_001286445.3	A2
RIPOR2	ENST00000259698.9	c.3106+71T>G		intron_variant		1		A2
RIPOR2	ENST00000538035.6	c.2956+71T>G		intron_variant		2		A2
RIPOR2	ENST00000613507.4	c.3106+71T>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46894 AN: 151774 Hom.: 8092 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.340 AC: 295181 AN: 869358 Hom.: 51330 AF XY: 0.344 AC XY: 154237 AN XY: 448922

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.659

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.309 AC: 46942 AN: 151892 Hom.: 8101 Cov.: 31 AF XY: 0.318 AC XY: 23598 AN XY: 74222

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.316

Alfa AF: 0.304 Hom.: 912

Bravo AF: 0.304

Asia WGS AF: 0.546 AC: 1894 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	-0.83
CADD	Benign	5.9
DANN	Benign	0.56

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: rs55640933; hg19: chr6-24809874; COSMIC: COSV52418652;