rs865999256
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000088.4(COL1A1):c.1393G>T(p.Glu465Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. E465E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000088.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.1393G>T | p.Glu465Ter | stop_gained | 21/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.1195G>T | p.Glu399Ter | stop_gained | 18/48 | ||
COL1A1 | XM_005257058.5 | c.1393G>T | p.Glu465Ter | stop_gained | 21/49 | ||
COL1A1 | XM_005257059.5 | c.957+1525G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.1393G>T | p.Glu465Ter | stop_gained | 21/51 | 1 | NM_000088.4 | P1 | |
COL1A1 | ENST00000471344.1 | n.337G>T | non_coding_transcript_exon_variant | 5/8 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1421916Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 704004
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type I Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 26, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 456733). This variant has not been reported in the literature in individuals affected with COL1A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu465*) in the COL1A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at