NM_001286445.3:c.3044-76A>T

Variant names:

• chr6-24806549-T-A
• rs9379689
• NM_001286445.3:c.3044-76A>T

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.3044-76A>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
• 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):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 104

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

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

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• 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=-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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286445.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPOR2	NM_001286445.3	MANE Select	c.3044-76A>T		intron	N/A	NP_001273374.1	A0A2R8YEE0
	RIPOR2	NM_014722.5		c.3107-76A>T		intron	N/A	NP_055537.2
	RIPOR2	NM_001346031.2		c.2957-76A>T		intron	N/A	NP_001332960.1	F5GX51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPOR2	ENST00000643898.2	MANE Select	c.3044-76A>T		intron	N/A	ENSP00000494268.2	A0A2R8YEE0
	RIPOR2	ENST00000259698.9	TSL:1	c.3107-76A>T		intron	N/A	ENSP00000259698.4	Q9Y4F9-1
	ENSG00000282804	ENST00000562221.1	TSL:5	c.83-76A>T		intron	N/A	ENSP00000455145.1	H3BP45

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

African (AFR) AF: 0.291 AC: 6032 AN: 20704

American (AMR) AF: 0.404 AC: 9094 AN: 22536

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 10369 AN: 19920

East Asian (EAS) AF: 0.214 AC: 6689 AN: 31280

South Asian (SAS) AF: 0.423 AC: 25613 AN: 60576

European-Finnish (FIN) AF: 0.516 AC: 22202 AN: 43054

Middle Eastern (MID) AF: 0.509 AC: 2329 AN: 4576

European-Non Finnish (NFE) AF: 0.532 AC: 366104 AN: 687830

Other (OTH) AF: 0.470 AC: 19782 AN: 42126

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

African (AFR) AF: 0.311 AC: 12905 AN: 41468

American (AMR) AF: 0.441 AC: 6734 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1849 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1032 AN: 5176

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

European-Finnish (FIN) AF: 0.521 AC: 5496 AN: 10540

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

European-Non Finnish (NFE) AF: 0.536 AC: 36404 AN: 67954

Other (OTH) AF: 0.421 AC: 889 AN: 2110

Alfa AF: 0.353 Hom.: 993

Bravo AF: 0.433

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.42
PhyloP100		-1.3
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: rs9379689; hg19: chr6-24806777; COSMIC: COSV52418575;