chr13-48303764-G-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000321.3(RB1):c.-149G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000801 in 1,248,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000321.3 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.-149G>T | 5_prime_UTR_variant | Exon 1 of 27 | ENST00000267163.6 | NP_000312.2 | ||
RB1 | NM_001407165.1 | c.-149G>T | 5_prime_UTR_variant | Exon 1 of 27 | NP_001394094.1 | |||
RB1 | NM_001407166.1 | c.-149G>T | 5_prime_UTR_variant | Exon 1 of 17 | NP_001394095.1 | |||
RB1 | NM_001407167.1 | c.-149G>T | 5_prime_UTR_variant | Exon 1 of 3 | NP_001394096.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000730 AC: 8AN: 1096490Hom.: 0 Cov.: 15 AF XY: 0.00000740 AC XY: 4AN XY: 540340
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74466
ClinVar
Submissions by phenotype
Retinoblastoma Uncertain:1Benign:1
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This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
not specified Uncertain:1
Variant summary: RB1 c.-149G>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 1.3e-05 in 150942 control chromosomes (gnomAD v3.1.2). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.-149G>T has been reported in the literature in an individual affected with Retinoblastoma (Macias_2008). This report does not provide unequivocal conclusions about association of the variant with Retinoblastoma. Experimental evidence demonstrated the variant significantly alters the UTR transcript structure (Kutchko_2015), however, does not allow convincing conclusions about the variant effect. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Malignant tumor of urinary bladder Uncertain:1
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not provided Uncertain:1
No data available from control populations to assess the frequency of this variant; Published functional studies demonstrate altered UTR transcript structure (Kutchko et al., 2015); This variant is associated with the following publications: (PMID: 20808897, 27569544, 18503160, 25999316) -
Hereditary cancer-predisposing syndrome Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at