17-50186913-C-CG
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000088.4(COL1A1):c.3540_3541insC(p.Gly1181ArgfsTer39) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,448 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. P1180P) 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 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.3540_3541insC | p.Gly1181ArgfsTer39 | frameshift_variant | 48/51 | ENST00000225964.10 | |
COL1A1 | XM_005257058.5 | c.3270_3271insC | p.Gly1091ArgfsTer39 | frameshift_variant | 46/49 | ||
COL1A1 | XM_005257059.5 | c.2622_2623insC | p.Gly875ArgfsTer39 | frameshift_variant | 35/38 | ||
COL1A1 | XM_011524341.2 | c.3342_3343insC | p.Gly1115ArgfsTer39 | frameshift_variant | 45/48 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.3540_3541insC | p.Gly1181ArgfsTer39 | frameshift_variant | 48/51 | 1 | NM_000088.4 | P1 | |
COL1A1 | ENST00000510710.3 | n.209_210insC | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461448Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 726990
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type I Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 01, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 456772). This premature translational stop signal has been observed in individual(s) with COL1A1-related conditions (PMID: 26138843). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly1181Argfs*39) 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