rs5918522

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.1245+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,204,044 control chromosomes in the GnomAD database, including 11,286 homozygotes. There are 59,827 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 911 hom., 4224 hem., cov: 23)

Exomes 𝑓: 0.16 ( 10375 hom. 55603 hem. )

Consequence

RPGR
NM_001034853.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -0.709

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), PanelApp Australia
RPGR-related retinopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
primary ciliary dyskinesia-retinitis pigmentosa syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
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=-0.92).

BP6

Variant X-38298940-T-C is Benign according to our data. Variant chrX-38298940-T-C is described in ClinVar as Benign. ClinVar VariationId is 98731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 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	UniProt
RPGR	NM_001034853.2	MANE Select	c.1245+16A>G	intron	N/A	NP_001030025.1	Q92834-6
RPGR	NM_000328.3		c.1245+16A>G	intron	N/A	NP_000319.1	Q92834-2
RPGR	NM_001367245.1		c.1242+16A>G	intron	N/A	NP_001354174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPGR	ENST00000645032.1	MANE Select	c.1245+16A>G	intron	N/A	ENSP00000495537.1	Q92834-6
ENSG00000250349	ENST00000465127.1	TSL:5	c.172-367181T>C	intron	N/A	ENSP00000417050.1	B4E171
RPGR	ENST00000494841.1	TSL:1	n.508+16A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

15112

AN:

111513

Hom.:

910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0903

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.000556

Gnomad SAS

AF:

0.0387

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.165

GnomAD2 exomes

AF:

0.123

AC:

22590

AN:

182946

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.0865

Gnomad AMR exome

AF:

0.0802

Gnomad ASJ exome

AF:

0.236

Gnomad EAS exome

AF:

0.000144

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.159

AC:

173275

AN:

1092481

Hom.:

10375

Cov.:

AF XY:

0.155

AC XY:

55603

AN XY:

358275

show subpopulations

African (AFR)

AF:

0.0886

AC:

2332

AN:

26308

American (AMR)

AF:

0.0856

AC:

3012

AN:

35183

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

4508

AN:

19343

East Asian (EAS)

AF:

0.000298

AC:

AN:

30183

South Asian (SAS)

AF:

0.0432

AC:

2337

AN:

54035

European-Finnish (FIN)

AF:

0.122

AC:

4950

AN:

40505

Middle Eastern (MID)

AF:

0.214

AC:

877

AN:

4098

European-Non Finnish (NFE)

AF:

0.177

AC:

148030

AN:

836892

Other (OTH)

AF:

0.157

AC:

7220

AN:

45934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

5046

10092

15138

20184

25230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5276

10552

15828

21104

26380

<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:

0.135

AC:

15102

AN:

111563

Hom.:

911

Cov.:

AF XY:

0.125

AC XY:

4224

AN XY:

33745

show subpopulations

African (AFR)

AF:

0.0901

AC:

2774

AN:

30775

American (AMR)

AF:

0.126

AC:

1321

AN:

10473

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

606

AN:

2640

East Asian (EAS)

AF:

0.000558

AC:

AN:

3586

South Asian (SAS)

AF:

0.0381

AC:

102

AN:

2676

European-Finnish (FIN)

AF:

0.110

AC:

658

AN:

5962

Middle Eastern (MID)

AF:

0.237

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.174

AC:

9235

AN:

53038

Other (OTH)

AF:

0.163

AC:

246

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

465

930

1394

1859

2324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.151

Hom.:

2463

Bravo

AF:

0.136

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.076

(source)

DANN

Benign

0.31

PhyloP100

-0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

Other links and lift over