6-24806524-A-C

Variant names:

• chr6-24806524-A-C
• rs4074420
• NM_001286445.3:c.3044-51T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

RIPOR2 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 104

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal dominant nonsyndromic hearing loss 21

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000282804 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.3044-51T>G		intron_variant	Intron 21 of 21	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.3044-51T>G		intron_variant	Intron 21 of 21		NM_001286445.3	ENSP00000494268.2
ENSG00000282804	ENST00000562221.1	c.83-51T>G		intron_variant	Intron 1 of 2	5		ENSP00000455145.1

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

African (AFR) AF: 0.300 AC: 7988 AN: 26622

American (AMR) AF: 0.419 AC: 12967 AN: 30984

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 12344 AN: 23368

East Asian (EAS) AF: 0.215 AC: 7303 AN: 33916

South Asian (SAS) AF: 0.431 AC: 31029 AN: 72006

European-Finnish (FIN) AF: 0.519 AC: 24539 AN: 47236

Middle Eastern (MID) AF: 0.514 AC: 2698 AN: 5252

European-Non Finnish (NFE) AF: 0.539 AC: 483616 AN: 897952

Other (OTH) AF: 0.476 AC: 24214 AN: 50850

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

African (AFR) AF: 0.311 AC: 12894 AN: 41468

American (AMR) AF: 0.441 AC: 6738 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1846 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1036 AN: 5184

South Asian (SAS) AF: 0.419 AC: 2021 AN: 4818

European-Finnish (FIN) AF: 0.521 AC: 5493 AN: 10542

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36399 AN: 67954

Other (OTH) AF: 0.422 AC: 890 AN: 2108

Alfa AF: 0.481 Hom.: 2351

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

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.33
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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