rs12663619
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001142800.2(EYS):c.4026C>T(p.Ser1342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,550,060 control chromosomes in the GnomAD database, including 13,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.10 ( 925 hom., cov: 32)
Exomes 𝑓: 0.13 ( 12922 hom. )
Consequence
EYS
NM_001142800.2 synonymous
NM_001142800.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0510
Genes affected
EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 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=-0.45).
BP6
?
Variant 6-64591841-G-A is Benign according to our data. Variant chr6-64591841-G-A is described in ClinVar as [Benign]. Clinvar id is 93609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-64591841-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.051 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EYS | NM_001142800.2 | c.4026C>T | p.Ser1342= | synonymous_variant | 26/43 | ENST00000503581.6 | |
EYS | NM_001292009.2 | c.4026C>T | p.Ser1342= | synonymous_variant | 26/44 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EYS | ENST00000503581.6 | c.4026C>T | p.Ser1342= | synonymous_variant | 26/43 | 5 | NM_001142800.2 | A2 | |
EYS | ENST00000370621.7 | c.4026C>T | p.Ser1342= | synonymous_variant | 26/44 | 1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.101 AC: 15356AN: 151962Hom.: 928 Cov.: 32
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GnomAD3 exomes AF: 0.118 AC: 18146AN: 153270Hom.: 1234 AF XY: 0.119 AC XY: 9671AN XY: 81272
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GnomAD4 exome AF: 0.132 AC: 184760AN: 1397980Hom.: 12922 Cov.: 35 AF XY: 0.132 AC XY: 90885AN XY: 689532
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GnomAD4 genome ? AF: 0.101 AC: 15351AN: 152080Hom.: 925 Cov.: 32 AF XY: 0.0994 AC XY: 7389AN XY: 74360
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 11, 2011 | 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. - |
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 | Eurofins Ntd Llc (ga) | Sep 19, 2013 | - - |
Retinitis pigmentosa Benign:2
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. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Retinitis pigmentosa 25 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Retinal dystrophy Benign:1
Benign, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at