chr14-21324652-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_020366.4(RPGRIP1):c.1797G>A(p.Pro599=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,613,316 control chromosomes in the GnomAD database, including 44,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.22 ( 3898 hom., cov: 32)
Exomes 𝑓: 0.23 ( 40242 hom. )
Consequence
RPGRIP1
NM_020366.4 synonymous
NM_020366.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.372
Genes affected
RPGRIP1 (HGNC:13436): (RPGR interacting protein 1) This gene encodes a photoreceptor protein that interacts with retinitis pigmentosa GTPase regulator protein and is a key component of cone and rod photoreceptor cells. Mutations in this gene lead to autosomal recessive congenital blindness. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 14-21324652-G-A is Benign according to our data. Variant chr14-21324652-G-A is described in ClinVar as [Benign]. Clinvar id is 99812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-21324652-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.372 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPGRIP1 | NM_020366.4 | c.1797G>A | p.Pro599= | synonymous_variant | 15/25 | ENST00000400017.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPGRIP1 | ENST00000400017.7 | c.1797G>A | p.Pro599= | synonymous_variant | 15/25 | 1 | NM_020366.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.220 AC: 33490AN: 152024Hom.: 3899 Cov.: 32
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GnomAD3 exomes AF: 0.207 AC: 51517AN: 249100Hom.: 6177 AF XY: 0.214 AC XY: 28949AN XY: 135174
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GnomAD4 exome AF: 0.230 AC: 335615AN: 1461174Hom.: 40242 Cov.: 34 AF XY: 0.231 AC XY: 167974AN XY: 726906
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GnomAD4 genome AF: 0.220 AC: 33522AN: 152142Hom.: 3898 Cov.: 32 AF XY: 0.219 AC XY: 16282AN XY: 74386
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ClinVar
Significance: Benign
Submissions summary: Benign:7Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 21, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Leber congenital amaurosis 6;C2750720:Cone-rod dystrophy 13 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cone-rod dystrophy 13 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Leber congenital amaurosis 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Other:1
not provided, no classification provided | literature only | Retina International | - | - - |
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