X-38323539-C-T

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.29-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,202,845 control chromosomes in the GnomAD database, including 14,961 homozygotes. There are 59,659 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 2750 hom., 7210 hem., cov: 22)

Exomes 𝑓: 0.14 ( 12211 hom. 52449 hem. )

Consequence

RPGR
NM_001034853.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.50

Publications

6 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=-0.86).

BP6

Variant X-38323539-C-T is Benign according to our data. Variant chrX-38323539-C-T is described in ClinVar as Benign. ClinVar VariationId is 92856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.29-15G>A		intron_variant	Intron 1 of 14	ENST00000645032.1	NP_001030025.1	Q92834-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1 link	c.29-15G>A		intron_variant	Intron 1 of 14		NM_001034853.2	ENSP00000495537.1		Q92834-6
ENSG00000250349	ENST00000465127.1 link	c.172-342582C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

24233

AN:

110988

Hom.:

2741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.0751

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0924

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.218

AC:

39354

AN:

180770

AF XY:

0.201

show subpopulations

Gnomad AFR exome

AF:

0.402

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.144

AC:

156798

AN:

1091805

Hom.:

12211

Cov.:

AF XY:

0.146

AC XY:

52449

AN XY:

359101

show subpopulations

African (AFR)

AF:

0.392

AC:

10256

AN:

26192

American (AMR)

AF:

0.314

AC:

10995

AN:

35065

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

2311

AN:

19317

East Asian (EAS)

AF:

0.640

AC:

19219

AN:

30047

South Asian (SAS)

AF:

0.294

AC:

15835

AN:

53817

European-Finnish (FIN)

AF:

0.107

AC:

4337

AN:

40411

Middle Eastern (MID)

AF:

0.0908

AC:

272

AN:

2996

European-Non Finnish (NFE)

AF:

0.102

AC:

85644

AN:

838198

Other (OTH)

AF:

0.173

AC:

7929

AN:

45762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

3849

7697

11546

15394

19243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3776

7552

11328

15104

18880

<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:

0.219

AC:

24275

AN:

111040

Hom.:

2750

Cov.:

AF XY:

0.216

AC XY:

7210

AN XY:

33316

show subpopulations

African (AFR)

AF:

0.388

AC:

11810

AN:

30435

American (AMR)

AF:

0.258

AC:

2713

AN:

10498

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

297

AN:

2641

East Asian (EAS)

AF:

0.619

AC:

2153

AN:

3476

South Asian (SAS)

AF:

0.319

AC:

848

AN:

2656

European-Finnish (FIN)

AF:

0.105

AC:

618

AN:

5913

Middle Eastern (MID)

AF:

0.0968

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.103

AC:

5470

AN:

53010

Other (OTH)

AF:

0.194

AC:

294

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

596

1191

1787

2382

2978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.142

Hom.:

4524

Bravo

AF:

0.243

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

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

- -

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.29-15G>A in intron 1 of RPGR: This variant is not expected to have clinical si gnificance because it has been identified in 39.3% (1508/3833) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs6651585). -

Jul 01, 2013

Eurofins Ntd Llc (ga)

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

- -

not provided

Benign:2

Mar 03, 2015

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.11

(source)

DANN

Benign

0.78

PhyloP100

-1.5

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over