6-24809543-A-G

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.3043+174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 152,186 control chromosomes in the GnomAD database, including 44,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.75 (44461 hom., cov: 32)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.119

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=-0.9).
• BP6: Variant 6-24809543-A-G is Benign according to our data. Variant chr6-24809543-A-G is described in ClinVar as [Benign]. Clinvar id is 1182577.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPOR2	NM_001286445.3	c.3043+174T>C		intron_variant		ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2	c.3043+174T>C		intron_variant			NM_001286445.3	A2
RIPOR2	ENST00000259698.9	c.3106+174T>C		intron_variant		1		A2
RIPOR2	ENST00000538035.6	c.2956+174T>C		intron_variant		2		A2
RIPOR2	ENST00000613507.4	c.3106+174T>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113395 AN: 152068 Hom.: 44439 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.746 AC: 113462 AN: 152186 Hom.: 44461 Cov.: 32 AF XY: 0.754 AC XY: 56098 AN XY: 74408

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.728

Alfa AF: 0.828 Hom.: 102077

Bravo AF: 0.724

Asia WGS AF: 0.831 AC: 2888 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

Mar 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	12
Dann	Benign	0.64

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: rs9379692; hg19: chr6-24809771;