rs2274321
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000329.3(RPE65):c.643+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,613,358 control chromosomes in the GnomAD database, including 1,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.032 ( 137 hom., cov: 32)
Exomes 𝑓: 0.025 ( 1031 hom. )
Consequence
RPE65
NM_000329.3 intron
NM_000329.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.352
Genes affected
RPE65 (HGNC:10294): (retinoid isomerohydrolase RPE65) The protein encoded by this gene is a component of the vitamin A visual cycle of the retina which supplies the 11-cis retinal chromophore of the photoreceptors opsin visual pigments. It is a member of the carotenoid cleavage oxygenase superfamily. All members of this superfamily are non-heme iron oxygenases with a seven-bladed propeller fold and oxidatively cleave carotenoid carbon:carbon double bonds. However, the protein encoded by this gene has acquired a divergent function that involves the concerted O-alkyl ester cleavage of its all-trans retinyl ester substrate and all-trans to 11-cis double bond isomerization of the retinyl moiety. As such, it performs the essential enzymatic isomerization step in the synthesis of 11-cis retinal. Mutations in this gene are associated with early-onset severe blinding disorders such as Leber congenital. [provided by RefSeq, Oct 2017]
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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=-0.59).
BP6
?
Variant 1-68440831-G-A is Benign according to our data. Variant chr1-68440831-G-A is described in ClinVar as [Benign]. Clinvar id is 255838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPE65 | NM_000329.3 | c.643+22C>T | intron_variant | ENST00000262340.6 | |||
LOC124904198 | XR_007066164.1 | n.72-7701G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPE65 | ENST00000262340.6 | c.643+22C>T | intron_variant | 1 | NM_000329.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0324 AC: 4931AN: 152126Hom.: 137 Cov.: 32
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GnomAD3 exomes AF: 0.0324 AC: 8127AN: 250972Hom.: 298 AF XY: 0.0364 AC XY: 4939AN XY: 135672
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GnomAD4 exome AF: 0.0253 AC: 37001AN: 1461114Hom.: 1031 Cov.: 31 AF XY: 0.0282 AC XY: 20491AN XY: 726894
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GnomAD4 genome ? AF: 0.0325 AC: 4941AN: 152244Hom.: 137 Cov.: 32 AF XY: 0.0336 AC XY: 2497AN XY: 74426
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Retinitis pigmentosa 87 with choroidal involvement Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Leber congenital amaurosis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
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