rs1801687
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001034853.2(RPGR):c.1274G>A(p.Arg425Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,205,424 control chromosomes in the GnomAD database, including 2,698 homozygotes. There are 26,057 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R425G) has been classified as Likely benign.
Frequency
Consequence
NM_001034853.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPGR | NM_001034853.2 | c.1274G>A | p.Arg425Lys | missense_variant | 11/15 | ENST00000645032.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPGR | ENST00000645032.1 | c.1274G>A | p.Arg425Lys | missense_variant | 11/15 | NM_001034853.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0932 AC: 10202AN: 109447Hom.: 506 Cov.: 21 AF XY: 0.0886 AC XY: 2822AN XY: 31837
GnomAD3 exomes AF: 0.101 AC: 18517AN: 182620Hom.: 1026 AF XY: 0.0912 AC XY: 6125AN XY: 67176
GnomAD4 exome AF: 0.0633 AC: 69387AN: 1095925Hom.: 2194 Cov.: 29 AF XY: 0.0642 AC XY: 23226AN XY: 361895
GnomAD4 genome ? AF: 0.0932 AC: 10210AN: 109499Hom.: 504 Cov.: 21 AF XY: 0.0887 AC XY: 2831AN XY: 31899
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 13, 2015 | p.Arg425Lys in exon 11 of RPGR: This variant is not expected to have clinical si gnificance because it has been identified in 15.4% (591/3833) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs1801687). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 24, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 11, 2024 | - - |
not provided Benign:1Other:2
not provided, no classification provided | literature only | Retina International | - | - - |
not provided, no classification provided | literature only | NEI Ophthalmic Genomics Laboratory, National Institutes of Health | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 26, 2014 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Retinal dystrophy Benign:1
Benign, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at