rs4084271

Variant names:

Variant summary

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

The NM_000328.3(RPGR):c.2241+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,169,750 control chromosomes in the GnomAD database, including 25,733 homozygotes. There are 88,469 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 1968 hom., 6438 hem., cov: 23)

Exomes 𝑓: 0.25 ( 23765 hom. 82031 hem. )

Consequence

RPGR
NM_000328.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

RPGR (HGNC:10295): (retinitis pigmentosa GTPase regulator) This gene encodes a protein with a series of six RCC1-like domains (RLDs), characteristic of the highly conserved guanine nucleotide exchange factors. The encoded protein is found in the Golgi body and interacts with RPGRIP1. This protein localizes to the outer segment of rod photoreceptors and is essential for their viability. Mutations in this gene have been associated with X-linked retinitis pigmentosa (XLRP). Multiple alternatively spliced transcript variants that encode different isoforms of this gene have been reported, but the full-length natures of only some have been determined. [provided by RefSeq, Dec 2008]

RPGR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-38273375-A-G is Benign according to our data. Variant chrX-38273375-A-G is described in ClinVar as [Benign]. Clinvar id is 227048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38273375-A-G is described in Lovd as [Likely_benign]. Variant chrX-38273375-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
RPGR	NM_000328.3 link	c.2241+11T>C	intron_variant	Intron 18 of 18	NP_000319.1	Q92834-2
RPGR	NM_001367245.1 link	c.2238+11T>C	intron_variant	Intron 18 of 18	NP_001354174.1
RPGR	NM_001367246.1 link	c.2055+11T>C	intron_variant	Intron 17 of 17	NP_001354175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250349	ENST00000465127.1 link	c.172-392746A>G		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

22374

AN:

111298

Hom.:

1968

Cov.:

AF XY:

0.192

AC XY:

6438

AN XY:

33510

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.294

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.00112

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.412

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.239

GnomAD3 exomes

AF:

0.197

AC:

31928

AN:

161709

Hom.:

2591

AF XY:

0.207

AC XY:

10734

AN XY:

51941

show subpopulations

Gnomad AFR exome

AF:

0.0942

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.000464

Gnomad SAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.246

AC:

260390

AN:

1058399

Hom.:

23765

Cov.:

AF XY:

0.245

AC XY:

82031

AN XY:

334153

show subpopulations

Gnomad4 AFR exome

AF:

0.0981

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.000567

Gnomad4 SAS exome

AF:

0.211

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.201

AC:

22361

AN:

111351

Hom.:

1968

Cov.:

AF XY:

0.192

AC XY:

6438

AN XY:

33573

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.361

Gnomad4 EAS

AF:

0.00112

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.268

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.259

Hom.:

14651

Bravo

AF:

0.192

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

2241+11T>C in intron 18A of RPGR: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 28.8% (1940/6727) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs4084271). -

Jan 11, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 3

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Macular degeneration, X-linked atrophic

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

X-linked cone-rod dystrophy 1

Benign:1

Nov 07, 2021

Genome-Nilou Lab

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

-0.57

CADD

Benign

DANN

Benign

0.83

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

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