rs80178653
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001034853.2(RPGR):c.1059+25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,157,980 control chromosomes in the GnomAD database, including 1,207 homozygotes. There are 13,490 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.031 ( 92 hom., 1209 hem., cov: 22)
Exomes 𝑓: 0.034 ( 1115 hom. 12281 hem. )
Consequence
RPGR
NM_001034853.2 intron
NM_001034853.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.684
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant X-38301222-A-G is Benign according to our data. Variant chrX-38301222-A-G is described in ClinVar as [Benign]. Clinvar id is 257191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPGR | NM_001034853.2 | c.1059+25T>C | intron_variant | ENST00000645032.1 | NP_001030025.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPGR | ENST00000645032.1 | c.1059+25T>C | intron_variant | NM_001034853.2 | ENSP00000495537 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0312 AC: 3480AN: 111660Hom.: 93 Cov.: 22 AF XY: 0.0356 AC XY: 1205AN XY: 33834
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GnomAD3 exomes AF: 0.0712 AC: 11344AN: 159227Hom.: 672 AF XY: 0.0669 AC XY: 3258AN XY: 48673
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GnomAD4 exome AF: 0.0342 AC: 35808AN: 1046264Hom.: 1115 Cov.: 23 AF XY: 0.0378 AC XY: 12281AN XY: 324502
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GnomAD4 genome AF: 0.0312 AC: 3483AN: 111716Hom.: 92 Cov.: 22 AF XY: 0.0357 AC XY: 1209AN XY: 33900
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at