chr1-68439684-A-AT
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2
The NM_000329.3(RPE65):c.644-43_644-42insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00632 in 1,259,218 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0068 ( 1 hom. )
Consequence
RPE65
NM_000329.3 intron
NM_000329.3 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.145
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 -8 ACMG points.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00252 (377/149640) while in subpopulation AFR AF= 0.00739 (302/40844). AF 95% confidence interval is 0.00671. There are 2 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPE65 | NM_000329.3 | c.644-43_644-42insA | intron_variant | ENST00000262340.6 | |||
LOC124904198 | XR_007066164.1 | n.72-8838dup | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPE65 | ENST00000262340.6 | c.644-43_644-42insA | intron_variant | 1 | NM_000329.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00253 AC: 378AN: 149542Hom.: 2 Cov.: 32
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GnomAD4 exome AF: 0.00684 AC: 7584AN: 1109578Hom.: 1 Cov.: 18 AF XY: 0.00633 AC XY: 3526AN XY: 557180
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GnomAD4 genome AF: 0.00252 AC: 377AN: 149640Hom.: 2 Cov.: 32 AF XY: 0.00220 AC XY: 161AN XY: 73036
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at