chr6-24891718-G-T

Variant names:

• chr6-24891718-G-T
• rs1007237
• NM_001286445.3:c.62-15901C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286445.3(RIPOR2):​c.62-15901C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,068 control chromosomes in the GnomAD database, including 39,920 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39920 hom., cov: 31)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 3 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
• 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
• autosomal recessive nonsyndromic hearing loss 104

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 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.62-15901C>A		intron	N/A	NP_001273374.1	A0A2R8YEE0
	RIPOR2	NM_014722.5		c.-26-15901C>A		intron	N/A	NP_055537.2
	RIPOR2	NM_001346031.2		c.-26-15901C>A		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.62-15901C>A		intron	N/A	ENSP00000494268.2	A0A2R8YEE0
	RIPOR2	ENST00000259698.9	TSL:1	c.-26-15901C>A		intron	N/A	ENSP00000259698.4	Q9Y4F9-1
	RIPOR2	ENST00000613507.4	TSL:5	c.-26-15901C>A		intron	N/A	ENSP00000482957.1	Q9Y4F9-1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108740 AN: 151950 Hom.: 39863 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.703

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.716 AC: 108853 AN: 152068 Hom.: 39920 Cov.: 31 AF XY: 0.716 AC XY: 53241 AN XY: 74326

African (AFR) AF: 0.888 AC: 36865 AN: 41512

American (AMR) AF: 0.713 AC: 10891 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2028 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3148 AN: 5174

South Asian (SAS) AF: 0.703 AC: 3390 AN: 4824

European-Finnish (FIN) AF: 0.687 AC: 7261 AN: 10562

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.634 AC: 43042 AN: 67940

Other (OTH) AF: 0.707 AC: 1488 AN: 2106

Alfa AF: 0.662 Hom.: 64642

Bravo AF: 0.720

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.75
DANN	Benign	0.77
PhyloP100		-0.57
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: rs1007237; hg19: chr6-24891946;