rs72667016
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_000088.4(COL1A1):c.432del(p.Gly145AspfsTer120) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000742 in 1,348,446 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P144P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000088.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.432del | p.Gly145AspfsTer120 | frameshift_variant | 5/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.432del | p.Gly145AspfsTer120 | frameshift_variant | 5/48 | ||
COL1A1 | XM_005257058.5 | c.432del | p.Gly145AspfsTer120 | frameshift_variant | 5/49 | ||
COL1A1 | XM_005257059.5 | c.432del | p.Gly145AspfsTer120 | frameshift_variant | 5/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.432del | p.Gly145AspfsTer120 | frameshift_variant | 5/51 | 1 | NM_000088.4 | P1 | |
COL1A1 | ENST00000507689.1 | downstream_gene_variant | 2 | ||||||
COL1A1 | ENST00000474644.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000742 AC: 10AN: 1348446Hom.: 0 Cov.: 31 AF XY: 0.00000455 AC XY: 3AN XY: 659150
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type I Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 03, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1357973). This variant is also known as p.P144fsX120. This premature translational stop signal has been observed in individual(s) with osteogenesis imperfecta (PMID: 16786509). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gly145Aspfs*120) 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