rs750581965
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting
The NM_000321.3(RB1):c.2106+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,609,962 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 -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.2106+8A>G | splice_region_variant, intron_variant | ENST00000267163.6 | |||
RB1 | NM_001407165.1 | c.2106+8A>G | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.2106+8A>G | splice_region_variant, intron_variant | 1 | NM_000321.3 | P1 | |||
RB1 | ENST00000643064.1 | c.194+78398A>G | intron_variant | ||||||
RB1 | ENST00000650461.1 | c.2106+8A>G | splice_region_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151714Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251346Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135846
GnomAD4 exome AF: 0.0000165 AC: 24AN: 1458248Hom.: 0 Cov.: 34 AF XY: 0.0000207 AC XY: 15AN XY: 725704
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151714Hom.: 0 Cov.: 30 AF XY: 0.0000405 AC XY: 3AN XY: 74062
ClinVar
Submissions by phenotype
Retinoblastoma Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at