rs745822791
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM1BP4_ModerateBP6_Very_StrongBS2_Supporting
The ENST00000267163.6(RB1):c.106G>A(p.Asp36Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,472,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D36G) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000267163.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.106G>A | p.Asp36Asn | missense_variant | 1/27 | ENST00000267163.6 | NP_000312.2 | |
RB1 | NM_001407165.1 | c.106G>A | p.Asp36Asn | missense_variant | 1/27 | NP_001394094.1 | ||
RB1 | NM_001407166.1 | c.106G>A | p.Asp36Asn | missense_variant | 1/17 | NP_001394095.1 | ||
RB1 | NM_001407167.1 | c.106G>A | p.Asp36Asn | missense_variant | 1/3 | NP_001394096.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.106G>A | p.Asp36Asn | missense_variant | 1/27 | 1 | NM_000321.3 | ENSP00000267163 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000920 AC: 7AN: 76124Hom.: 0 AF XY: 0.0000908 AC XY: 4AN XY: 44042
GnomAD4 exome AF: 0.0000424 AC: 56AN: 1319918Hom.: 0 Cov.: 31 AF XY: 0.0000430 AC XY: 28AN XY: 650728
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74320
ClinVar
Submissions by phenotype
Retinoblastoma Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jul 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 28, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2020 | 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