15-89210068-T-G
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000326.5(RLBP1):c.*217A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 591,350 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0029 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00034 ( 1 hom. )
Consequence
RLBP1
NM_000326.5 3_prime_UTR
NM_000326.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0360
Genes affected
RLBP1 (HGNC:10024): (retinaldehyde binding protein 1) The protein encoded by this gene is a 36-kD water-soluble protein which carries 11-cis-retinaldehyde or 11-cis-retinal as physiologic ligands. It may be a functional component of the visual cycle. Mutations of this gene have been associated with severe rod-cone dystrophy, Bothnia dystrophy (nonsyndromic autosomal recessive retinitis pigmentosa) and retinitis punctata albescens. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 15-89210068-T-G is Benign according to our data. Variant chr15-89210068-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 887403.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00294 (448/152296) while in subpopulation AFR AF= 0.0104 (432/41572). AF 95% confidence interval is 0.00958. There are 3 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RLBP1 | NM_000326.5 | c.*217A>C | 3_prime_UTR_variant | 9/9 | ENST00000268125.10 | NP_000317.1 | ||
RLBP1 | XM_011521870.3 | c.*217A>C | 3_prime_UTR_variant | 9/9 | XP_011520172.1 | |||
RLBP1 | XM_047432927.1 | c.*217A>C | 3_prime_UTR_variant | 7/7 | XP_047288883.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RLBP1 | ENST00000268125 | c.*217A>C | 3_prime_UTR_variant | 9/9 | 1 | NM_000326.5 | ENSP00000268125.5 | |||
RLBP1 | ENST00000563254 | c.*217A>C | 3_prime_UTR_variant | 3/3 | 2 | ENSP00000454740.1 |
Frequencies
GnomAD3 genomes AF: 0.00294 AC: 447AN: 152178Hom.: 3 Cov.: 33
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GnomAD4 exome AF: 0.000342 AC: 150AN: 439054Hom.: 1 Cov.: 4 AF XY: 0.000324 AC XY: 75AN XY: 231232
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GnomAD4 genome AF: 0.00294 AC: 448AN: 152296Hom.: 3 Cov.: 33 AF XY: 0.00277 AC XY: 206AN XY: 74470
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Retinitis pigmentosa Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Pigmentary retinal dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Newfoundland cone-rod dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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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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