13-48364886-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_000321.3(RB1):c.862-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000413 in 1,550,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000321.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.862-8T>C | splice_region_variant, intron_variant | ENST00000267163.6 | NP_000312.2 | |||
RB1 | NM_001407165.1 | c.862-8T>C | splice_region_variant, intron_variant | NP_001394094.1 | ||||
RB1 | NM_001407166.1 | c.862-8T>C | splice_region_variant, intron_variant | NP_001394095.1 | ||||
LOC112268118 | XR_002957522.2 | n.212A>G | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.862-8T>C | splice_region_variant, intron_variant | 1 | NM_000321.3 | ENSP00000267163.4 | ||||
RB1 | ENST00000650461.1 | c.862-8T>C | splice_region_variant, intron_variant | ENSP00000497193.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 2AN: 165442Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 87754
GnomAD4 exome AF: 0.0000451 AC: 63AN: 1398144Hom.: 0 Cov.: 30 AF XY: 0.0000406 AC XY: 28AN XY: 690030
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
Retinoblastoma Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 20, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 18, 2023 | - - |
RB1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 04, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at