rs4084271

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 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:

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=-0.57).

BP6

Variant X-38273375-A-G is Benign according to our data. Variant chrX-38273375-A-G is described in ClinVar as Benign. ClinVar VariationId is 227048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000328.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
RPGR	NM_000328.3	c.2241+11T>C	intron	N/A	NP_000319.1	Q92834-2
RPGR	NM_001367245.1	c.2238+11T>C	intron	N/A	NP_001354174.1
RPGR	NM_001367246.1	c.2055+11T>C	intron	N/A	NP_001354175.1	Q92834-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000250349	ENST00000465127.1	TSL:5	c.172-392746A>G	intron	N/A	ENSP00000417050.1	B4E171
RPGR	ENST00000339363.7	TSL:5	c.2856+11T>C	intron	N/A	ENSP00000343671.3	Q92834-1
RPGR	ENST00000642395.2		c.2241+11T>C	intron	N/A	ENSP00000493468.2	Q92834-2

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

22374

AN:

111298

Hom.:

1968

Cov.:

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

GnomAD2 exomes

AF:

0.197

AC:

31928

AN:

161709

AF XY:

0.207

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 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

African (AFR)

AF:

0.0981

AC:

2535

AN:

25844

American (AMR)

AF:

0.113

AC:

3852

AN:

34083

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

6896

AN:

18980

East Asian (EAS)

AF:

0.000567

AC:

AN:

29982

South Asian (SAS)

AF:

0.211

AC:

11042

AN:

52242

European-Finnish (FIN)

AF:

0.204

AC:

8045

AN:

39385

Middle Eastern (MID)

AF:

0.385

AC:

1324

AN:

3438

European-Non Finnish (NFE)

AF:

0.267

AC:

215880

AN:

809737

Other (OTH)

AF:

0.242

AC:

10799

AN:

44708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

5794

11588

17381

23175

28969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7398

14796

22194

29592

36990

<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:

0.201

AC:

22361

AN:

111351

Hom.:

1968

Cov.:

AF XY:

0.192

AC XY:

6438

AN XY:

33573

show subpopulations

African (AFR)

AF:

0.101

AC:

3121

AN:

30797

American (AMR)

AF:

0.169

AC:

1775

AN:

10495

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

954

AN:

2641

East Asian (EAS)

AF:

0.00112

AC:

AN:

3567

South Asian (SAS)

AF:

0.200

AC:

533

AN:

2666

European-Finnish (FIN)

AF:

0.201

AC:

1185

AN:

5908

Middle Eastern (MID)

AF:

0.408

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.268

AC:

14146

AN:

52869

Other (OTH)

AF:

0.235

AC:

357

AN:

1519

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

658

1316

1975

2633

3291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.251

Hom.:

18316

Bravo

AF:

0.192

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Macular degeneration, X-linked atrophic (1)

Primary ciliary dyskinesia (1)

Retinitis pigmentosa 3 (1)

X-linked cone-rod dystrophy 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

2.4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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