rs4084271
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000339363.7(RPGR):c.2856+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
ENST00000339363.7 intron
ENST00000339363.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.42
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 id is 227048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38273375-A-G is described in Lovd as [Likely_benign]. Variant chrX-38273375-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPGR | NM_000328.3 | c.2241+11T>C | intron_variant | NP_000319.1 | ||||
RPGR | NM_001367245.1 | c.2238+11T>C | intron_variant | NP_001354174.1 | ||||
RPGR | NM_001367246.1 | c.2055+11T>C | intron_variant | NP_001354175.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPGR | ENST00000339363.7 | c.2856+11T>C | intron_variant | 5 | ENSP00000343671 | P4 | ||||
RPGR | ENST00000642395.2 | c.2241+11T>C | intron_variant | ENSP00000493468 | A2 | |||||
RPGR | ENST00000644238.1 | c.1722+11T>C | intron_variant | ENSP00000496728 |
Frequencies
GnomAD3 genomes AF: 0.201 AC: 22374AN: 111298Hom.: 1968 Cov.: 23 AF XY: 0.192 AC XY: 6438AN XY: 33510
GnomAD3 genomes
AF:
AC:
22374
AN:
111298
Hom.:
Cov.:
23
AF XY:
AC XY:
6438
AN XY:
33510
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.197 AC: 31928AN: 161709Hom.: 2591 AF XY: 0.207 AC XY: 10734AN XY: 51941
GnomAD3 exomes
AF:
AC:
31928
AN:
161709
Hom.:
AF XY:
AC XY:
10734
AN XY:
51941
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.246 AC: 260390AN: 1058399Hom.: 23765 Cov.: 23 AF XY: 0.245 AC XY: 82031AN XY: 334153
GnomAD4 exome
AF:
AC:
260390
AN:
1058399
Hom.:
Cov.:
23
AF XY:
AC XY:
82031
AN XY:
334153
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.201 AC: 22361AN: 111351Hom.: 1968 Cov.: 23 AF XY: 0.192 AC XY: 6438AN XY: 33573
GnomAD4 genome
AF:
AC:
22361
AN:
111351
Hom.:
Cov.:
23
AF XY:
AC XY:
6438
AN XY:
33573
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 11, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | 2241+11T>C in intron 18A of RPGR: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 28.8% (1940/6727) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs4084271). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Retinitis pigmentosa 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Macular degeneration, X-linked atrophic Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
X-linked cone-rod dystrophy 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at