X-38290948-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001034853.2(RPGR):c.1572+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 952,665 control chromosomes in the GnomAD database, including 2,328 homozygotes. There are 17,309 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.094 ( 509 hom., 2926 hem., cov: 21)

Exomes 𝑓: 0.061 ( 1819 hom. 14383 hem. )

Consequence

RPGR
NM_001034853.2 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:8O:1

Conservation

PhyloP100: -1.07

Publications

2 publications found

Variant links:

Genes affected

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa 3
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
RPGR-related retinopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
primary ciliary dyskinesia-retinitis pigmentosa syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
macular degeneration, X-linked atrophic
Inheritance: XL Classification: LIMITED Submitted by: G2P

RPGR links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant X-38290948-T-C is Benign according to our data. Variant chrX-38290948-T-C is described in ClinVar as Benign. ClinVar VariationId is 92852.Status of the report is reviewed_by_expert_panel, 3 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034853.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPGR	NM_001034853.2	MANE Select	c.1572+11A>G	intron	N/A	NP_001030025.1
RPGR	NM_000328.3		c.1572+11A>G	intron	N/A	NP_000319.1
RPGR	NM_001367245.1		c.1569+11A>G	intron	N/A	NP_001354174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPGR	ENST00000645032.1	MANE Select	c.1572+11A>G	intron	N/A	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1	TSL:5	c.172-375173T>C	intron	N/A	ENSP00000417050.1
RPGR	ENST00000339363.7	TSL:5	c.1572+11A>G	intron	N/A	ENSP00000343671.3

Frequencies

GnomAD3 genomes

AF:

0.0941

AC:

10285

AN:

109315

Hom.:

511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.0677

Gnomad EAS

AF:

0.0753

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0935

Gnomad MID

AF:

0.0702

Gnomad NFE

AF:

0.0490

Gnomad OTH

AF:

0.0729

GnomAD2 exomes

AF:

0.0985

AC:

16562

AN:

168178

AF XY:

0.0850

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.232

Gnomad ASJ exome

AF:

0.0625

Gnomad EAS exome

AF:

0.0677

Gnomad FIN exome

AF:

0.0945

Gnomad NFE exome

AF:

0.0460

Gnomad OTH exome

AF:

0.0745

GnomAD4 exome

AF:

0.0611

AC:

51506

AN:

843332

Hom.:

1819

Cov.:

AF XY:

0.0623

AC XY:

14383

AN XY:

230904

show subpopulations

African (AFR)

AF:

0.159

AC:

3396

AN:

21298

American (AMR)

AF:

0.218

AC:

7037

AN:

32212

Ashkenazi Jewish (ASJ)

AF:

0.0577

AC:

922

AN:

15978

East Asian (EAS)

AF:

0.0770

AC:

2024

AN:

26294

South Asian (SAS)

AF:

0.139

AC:

5769

AN:

41433

European-Finnish (FIN)

AF:

0.0895

AC:

3152

AN:

35218

Middle Eastern (MID)

AF:

0.0700

AC:

241

AN:

3442

European-Non Finnish (NFE)

AF:

0.0422

AC:

26667

AN:

631323

Other (OTH)

AF:

0.0636

AC:

2298

AN:

36134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1370

2740

4109

5479

6849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1150

2300

3450

4600

5750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0941

AC:

10291

AN:

109333

Hom.:

509

Cov.:

AF XY:

0.0920

AC XY:

2926

AN XY:

31795

show subpopulations

African (AFR)

AF:

0.160

AC:

4825

AN:

30230

American (AMR)

AF:

0.130

AC:

1315

AN:

10110

Ashkenazi Jewish (ASJ)

AF:

0.0677

AC:

178

AN:

2630

East Asian (EAS)

AF:

0.0756

AC:

267

AN:

3531

South Asian (SAS)

AF:

0.143

AC:

372

AN:

2602

European-Finnish (FIN)

AF:

0.0935

AC:

497

AN:

5317

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.0490

AC:

2574

AN:

52545

Other (OTH)

AF:

0.0721

AC:

107

AN:

1484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

322

643

965

1286

1608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0861

Hom.:

1279

Bravo

AF:

0.104

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:4

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 15, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

not provided

Benign:2Other:1

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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

RPGR-related retinopathy

Benign:1

Sep 07, 2025

ClinGen X-linked Inherited Retinal Disease Variant Curation Expert Panel, ClinGen

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

NM_001034853.2(RPGR):c.1572+11A>G is a non-coding variant within intron 13 that is located outside of the splice donor region (BP7). The splicing impact predictor SpliceAI gives a delta score of 0.00 for all predictive splice changes, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4). This variant is present in gnomAD v4.1.0 at a frequency of 0.0658891 among hemizygous individuals, with 17,309 variant alleles / 262,699 total hemizygous alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1). In summary, this variant is classified as benign for RPGR-related retinopathy based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0; BA1, BP4, and BP7.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.52

(source)

DANN

Benign

0.35

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over