rs1470523018
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_000321.3(RB1):c.1139A>G(p.Asn380Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000101 in 1,588,354 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N380D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000321.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.1139A>G | p.Asn380Ser | missense_variant | 12/27 | ENST00000267163.6 | |
LOC112268118 | XR_002957522.2 | n.121+744T>C | intron_variant, non_coding_transcript_variant | ||||
RB1 | NM_001407165.1 | c.1139A>G | p.Asn380Ser | missense_variant | 12/27 | ||
RB1 | NM_001407166.1 | c.1139A>G | p.Asn380Ser | missense_variant | 12/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.1139A>G | p.Asn380Ser | missense_variant | 12/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.1139A>G | p.Asn380Ser | missense_variant | 12/27 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250688Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135506
GnomAD4 exome AF: 0.00000975 AC: 14AN: 1436234Hom.: 0 Cov.: 28 AF XY: 0.0000112 AC XY: 8AN XY: 716084
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74316
ClinVar
Submissions by phenotype
Retinoblastoma Uncertain:2Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 15, 2023 | This missense variant replaces asparagine with serine at codon 380 of the RB1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RB1-related disorders in the literature. This variant has been identified in 2/282042 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2024 | The p.N380S variant (also known as c.1139A>G), located in coding exon 12 of the RB1 gene, results from an A to G substitution at nucleotide position 1139. The asparagine at codon 380 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at