Variant rs9358799 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000562221.1(ENSG00000282804):c.*6+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,524,680 control chromosomes in the GnomAD database, including 200,409 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16113 hom., cov: 32)

Exomes 𝑓: 0.51 ( 184296 hom. )

Consequence

ENSG00000282804
ENST00000562221.1 splice_donor, intron

Scores

Splicing: ADA: 0.01401

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.390

Variant links:

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 links:

ENSG00000282804 (HGNC:):

ENSG00000282804 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 6-24806366-C-T is Benign according to our data. Variant chr6-24806366-C-T is described in ClinVar as [Benign]. Clinvar id is 517548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 link	c.*7G>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000643898.2	NP_001273374.1	A0A2R8YEE0B7Z5J9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898 link	c.*7G>A		3_prime_UTR_variant	Exon 22 of 22		NM_001286445.3	ENSP00000494268.2		A0A2R8YEE0
ENSG00000282804	ENST00000562221.1 link	c.*6+1G>A		splice_donor_variant, intron_variant	Intron 2 of 2	5		ENSP00000455145.1		H3BP45

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67887

AN:

151832

Hom.:

16113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.427

GnomAD3 exomes

AF:

0.465

AC:

72494

AN:

155784

Hom.:

17748

AF XY:

0.469

AC XY:

38739

AN XY:

82556

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.534

Gnomad EAS exome

AF:

0.200

Gnomad SAS exome

AF:

0.437

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.541

Gnomad OTH exome

AF:

0.480

GnomAD4 exome

AF:

0.512

AC:

703348

AN:

1372730

Hom.:

184296

Cov.:

AF XY:

0.512

AC XY:

347178

AN XY:

678548

show subpopulations

Gnomad4 AFR exome

AF:

0.299

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.531

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.432

Gnomad4 FIN exome

AF:

0.520

Gnomad4 NFE exome

AF:

0.539

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

AF:

0.447

AC:

67923

AN:

151950

Hom.:

16113

Cov.:

AF XY:

0.446

AC XY:

33136

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.311

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.533

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.420

Gnomad4 FIN

AF:

0.522

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.422

Alfa

AF:

0.510

Hom.:

23479

Bravo

AF:

0.433

Asia WGS

AF:

0.298

AC:

1037

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.*7G>A in exon 23 of FAM65B: This variant is not expected to have clinical sign ificance because it has been identified in 52.33% (4623/8834) of European chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs9358799). -

Autosomal recessive nonsyndromic hearing loss 104

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

May 09, 2017

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

-0.65

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.014

dbscSNV1_RF

Benign

0.15

SpliceAI score (max)

0.93

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.93

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over