6-24806047-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001286445.3(RIPOR2):c.*326A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 245,256 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (0 hom.)
• Consequence: RIPOR2 NM_001286445.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.547

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=-0.88).
• BP6: Variant 6-24806047-T-C is Benign according to our data. Variant chr6-24806047-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1316858.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1642/152220) while in subpopulation AFR AF= 0.0312 (1295/41528). AF 95% confidence interval is 0.0298. There are 17 homozygotes in gnomad4. There are 800 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPOR2	NM_001286445.3	c.*326A>G		3_prime_UTR_variant	22/22	ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2	c.*326A>G		3_prime_UTR_variant	22/22		NM_001286445.3	A2
RIPOR2	ENST00000259698.9	c.*326A>G		3_prime_UTR_variant	23/23	1		A2
RIPOR2	ENST00000538035.6	c.*326A>G		3_prime_UTR_variant	22/22	2		A2
RIPOR2	ENST00000613507.4	c.*326A>G		3_prime_UTR_variant	23/23	5		A2

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1623 AN: 152102 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.00259 AC: 241 AN: 93036 Hom.: 0 Cov.: 0 AF XY: 0.00249 AC XY: 120 AN XY: 48118

Gnomad4 AFR exome AF: 0.0200

Gnomad4 AMR exome AF: 0.00518

Gnomad4 ASJ exome AF: 0.00224

Gnomad4 EAS exome AF: 0.000247

Gnomad4 SAS exome AF: 0.00254

Gnomad4 FIN exome AF: 0.000965

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.00371

GnomAD4 genome AF: 0.0108 AC: 1642 AN: 152220 Hom.: 17 Cov.: 32 AF XY: 0.0107 AC XY: 800 AN XY: 74422

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.00798

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.00770 Hom.: 0

Bravo AF: 0.0124

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 16, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.6
Dann	Benign	0.82

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: rs113707390; hg19: chr6-24806275;