rs34116882
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_020366.4(RPGRIP1):c.3546C>T(p.Asp1182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,611,240 control chromosomes in the GnomAD database, including 420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 24 hom., cov: 32)
Exomes 𝑓: 0.022 ( 396 hom. )
Consequence
RPGRIP1
NM_020366.4 synonymous
NM_020366.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0360
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 14-21345126-C-T is Benign according to our data. Variant chr14-21345126-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 99820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-21345126-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.036 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0154 (2344/152256) while in subpopulation NFE AF= 0.0249 (1692/68014). AF 95% confidence interval is 0.0239. There are 24 homozygotes in gnomad4. There are 1103 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 24 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPGRIP1 | NM_020366.4 | c.3546C>T | p.Asp1182= | synonymous_variant | 23/25 | ENST00000400017.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPGRIP1 | ENST00000400017.7 | c.3546C>T | p.Asp1182= | synonymous_variant | 23/25 | 1 | NM_020366.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0154 AC: 2344AN: 152138Hom.: 24 Cov.: 32
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GnomAD3 exomes AF: 0.0168 AC: 4173AN: 249058Hom.: 46 AF XY: 0.0167 AC XY: 2255AN XY: 135118
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GnomAD4 exome AF: 0.0222 AC: 32421AN: 1458984Hom.: 396 Cov.: 29 AF XY: 0.0218 AC XY: 15798AN XY: 725938
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GnomAD4 genome ? AF: 0.0154 AC: 2344AN: 152256Hom.: 24 Cov.: 32 AF XY: 0.0148 AC XY: 1103AN XY: 74446
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 31, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 28, 2023 | - - |
not provided, no classification provided | literature only | Retina International | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Leber congenital amaurosis 6;C2750720:Cone-rod dystrophy 13 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 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
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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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