X-38275043-G-A

Variant names:

Variant summary

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

The ENST00000465127.1(ENSG00000250349):c.172-391078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 963,272 control chromosomes in the GnomAD database, including 1,001 homozygotes. There are 12,345 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 87 hom., 1032 hem., cov: 22)

Exomes 𝑓: 0.050 ( 914 hom. 11313 hem. )

Consequence

ENSG00000250349
ENST00000465127.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.39

Publications

1 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)
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:

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=-0.97).

BP6

Variant X-38275043-G-A is Benign according to our data. Variant chrX-38275043-G-A is described in ClinVar as Benign. ClinVar VariationId is 255834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
RPGR	NM_000328.3 link	c.2149+46C>T	intron_variant	Intron 17 of 18	NP_000319.1	Q92834-2
RPGR	NM_001367245.1 link	c.2146+46C>T	intron_variant	Intron 17 of 18	NP_001354174.1
RPGR	NM_001367246.1 link	c.1963+46C>T	intron_variant	Intron 16 of 17	NP_001354175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250349	ENST00000465127.1 link	c.172-391078G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0362

AC:

4014

AN:

110956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00750

Gnomad AMI

AF:

0.0562

Gnomad AMR

AF:

0.0225

Gnomad ASJ

AF:

0.0353

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0378

Gnomad MID

AF:

0.0170

Gnomad NFE

AF:

0.0587

Gnomad OTH

AF:

0.0370

GnomAD2 exomes

AF:

0.0372

AC:

6371

AN:

171074

AF XY:

0.0356

show subpopulations

Gnomad AFR exome

AF:

0.00632

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0446

Gnomad EAS exome

AF:

0.0000753

Gnomad FIN exome

AF:

0.0424

Gnomad NFE exome

AF:

0.0585

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0502

AC:

42765

AN:

852268

Hom.:

914

Cov.:

AF XY:

0.0474

AC XY:

11313

AN XY:

238542

show subpopulations

African (AFR)

AF:

0.00613

AC:

133

AN:

21687

American (AMR)

AF:

0.0158

AC:

546

AN:

34652

Ashkenazi Jewish (ASJ)

AF:

0.0432

AC:

771

AN:

17863

East Asian (EAS)

AF:

0.0000690

AC:

AN:

28986

South Asian (SAS)

AF:

0.0233

AC:

1132

AN:

48677

European-Finnish (FIN)

AF:

0.0455

AC:

1786

AN:

39222

Middle Eastern (MID)

AF:

0.00979

AC:

AN:

3574

European-Non Finnish (NFE)

AF:

0.0594

AC:

36787

AN:

619599

Other (OTH)

AF:

0.0414

AC:

1573

AN:

38008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1484

2968

4451

5935

7419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1204

2408

3612

4816

6020

<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:

0.0362

AC:

4016

AN:

111004

Hom.:

Cov.:

AF XY:

0.0310

AC XY:

1032

AN XY:

33280

show subpopulations

African (AFR)

AF:

0.00748

AC:

229

AN:

30615

American (AMR)

AF:

0.0225

AC:

235

AN:

10459

Ashkenazi Jewish (ASJ)

AF:

0.0353

AC:

AN:

2638

East Asian (EAS)

AF:

0.000281

AC:

AN:

3563

South Asian (SAS)

AF:

0.0141

AC:

AN:

2626

European-Finnish (FIN)

AF:

0.0378

AC:

221

AN:

5840

Middle Eastern (MID)

AF:

0.0140

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.0587

AC:

3104

AN:

52867

Other (OTH)

AF:

0.0365

AC:

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

150

300

451

601

751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0444

Hom.:

359

Bravo

AF:

0.0332

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

- -

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

-0.97

CADD

Benign

0.034

(source)

DANN

Benign

0.16

PhyloP100

-1.4

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

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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