6-24806524-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.3044-51T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,340,190 control chromosomes in the GnomAD database, including 174,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16099 hom., cov: 32)
  • Exomes 𝑓: 0.51 (158657 hom.)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.397

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=-0.93).
• BP6: Variant 6-24806524-A-C is Benign according to our data. Variant chr6-24806524-A-C is described in ClinVar as [Benign]. Clinvar id is 1268179.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	UniProt
RIPOR2	NM_001286445.3	c.3044-51T>G		intron_variant		ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2	c.3044-51T>G		intron_variant			NM_001286445.3	A2
RIPOR2	ENST00000259698.9	c.3107-51T>G		intron_variant		1		A2
RIPOR2	ENST00000538035.6	c.2957-51T>G		intron_variant		2		A2
RIPOR2	ENST00000613507.4	c.3107-51T>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67877 AN: 151892 Hom.: 16099 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.200

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: 0.511 AC: 606698 AN: 1188186 Hom.: 158657 AF XY: 0.510 AC XY: 301825 AN XY: 592386

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.447 AC: 67912 AN: 152004 Hom.: 16099 Cov.: 32 AF XY: 0.446 AC XY: 33117 AN XY: 74298

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.422

Alfa AF: 0.488 Hom.: 2315

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.4
Dann	Benign	0.33

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: rs4074420; hg19: chr6-24806752; COSMIC: COSV52418570;