rs1010049143
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000321.3(RB1):c.138-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,716 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, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.138-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000267163.6 | |||
RB1 | NM_001407165.1 | c.138-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
RB1 | NM_001407166.1 | c.138-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
RB1 | NM_001407167.1 | c.138-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.138-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000321.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251118Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135744
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1448716Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 721540
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Retinoblastoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 30, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at