chr6-24806366-C-T

Variant names:

• chr6-24806366-C-T
• rs9358799
• NM_001286445.3:c.*7G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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

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]

ENSG00000282804 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	c.*7G>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000643898.2	NP_001273374.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67887 AN: 151832 Hom.: 16113 Cov.: 32

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

GnomAD2 exomes AF: 0.465 AC: 72494 AN: 155784 AF XY: 0.469

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 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.: 24 AF XY: 0.512 AC XY: 347178 AN XY: 678548

Gnomad4 AFR exome AF: 0.299 AC: 9314 AN: 31112

Gnomad4 AMR exome AF: 0.421 AC: 14949 AN: 35492

Gnomad4 ASJ exome AF: 0.531 AC: 13254 AN: 24974

Gnomad4 EAS exome AF: 0.215 AC: 7675 AN: 35640

Gnomad4 SAS exome AF: 0.432 AC: 33977 AN: 78578

Gnomad4 FIN exome AF: 0.520 AC: 25611 AN: 49230

Gnomad4 NFE exome AF: 0.539 AC: 568351 AN: 1054966

Gnomad4 Remaining exome AF: 0.478 AC: 27296 AN: 57074

GnomAD4 genome AF: 0.447 AC: 67923 AN: 151950 Hom.: 16113 Cov.: 32 AF XY: 0.446 AC XY: 33136 AN XY: 74264

Gnomad4 AFR AF: 0.311 AC: 0.311061 AN: 0.311061

Gnomad4 AMR AF: 0.441 AC: 0.441473 AN: 0.441473

Gnomad4 ASJ AF: 0.533 AC: 0.532872 AN: 0.532872

Gnomad4 EAS AF: 0.200 AC: 0.199729 AN: 0.199729

Gnomad4 SAS AF: 0.420 AC: 0.419602 AN: 0.419602

Gnomad4 FIN AF: 0.522 AC: 0.522127 AN: 0.522127

Gnomad4 NFE AF: 0.536 AC: 0.535793 AN: 0.535793

Gnomad4 OTH AF: 0.422 AC: 0.421727 AN: 0.421727

Alfa AF: 0.492 Hom.: 32699

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

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	11
DANN	Benign	0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9358799; hg19: chr6-24806594; COSMIC: COSV52418565;