8-54616061-T-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001375654.1(RP1):c.-12-4894T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 152,316 control chromosomes in the GnomAD database, including 451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.042 ( 451 hom., cov: 33)
Failed GnomAD Quality Control
Consequence
RP1
NM_001375654.1 intron
NM_001375654.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.25
Genes affected
RP1 (HGNC:10263): (RP1 axonemal microtubule associated) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two doublecortin domains, which bind microtubules and regulate microtubule polymerization. The encoded protein is a photoreceptor microtubule-associated protein and is required for correct stacking of outer segment disc. This protein and the RP1L1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Because of its response to in vivo retinal oxygen levels, this protein was initially named ORP1 (oxygen-regulated protein-1). This protein was subsequently designated RP1 (retinitis pigmentosa 1) when it was found that mutations in this gene cause autosomal dominant retinitis pigmentosa. Mutations in this gene also cause autosomal recessive retinitis pigmentosa. Transcript variants resulted from an alternative promoter and alternative splicings have been found, which overlap the current reference sequence and has several exons upstream and downstream of the current reference sequence. However, the biological validity and full-length nature of some variants cannot be determined at this time.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
Variant 8-54616061-T-C is Benign according to our data. Variant chr8-54616061-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 369611.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RP1 | NM_006269.2 | upstream_gene_variant | ENST00000220676.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RP1 | ENST00000636932.1 | c.-12-4894T>C | intron_variant | 5 | |||||
RP1 | ENST00000220676.2 | upstream_gene_variant | 1 | NM_006269.2 | |||||
RP1 | ENST00000637698.1 | upstream_gene_variant | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0422 AC: 6423AN: 152198Hom.: 450 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSRAC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
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Data not reliable, filtered out with message: AC0;AS_VQSR
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GnomAD4 genome ? AF: 0.0422 AC: 6433AN: 152316Hom.: 451 Cov.: 33 AF XY: 0.0413 AC XY: 3074AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis Pigmentosa, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at