rs760094345
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000494.4(COL17A1):c.214C>T(p.Arg72Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000494.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL17A1 | NM_000494.4 | c.214C>T | p.Arg72Ter | stop_gained | 5/56 | ENST00000648076.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL17A1 | ENST00000648076.2 | c.214C>T | p.Arg72Ter | stop_gained | 5/56 | NM_000494.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251454Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135896
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461808Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727206
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Junctional epidermolysis bullosa, non-Herlitz type Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota | Jun 01, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change creates a premature translational stop signal (p.Arg72*) in the COL17A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL17A1 are known to be pathogenic (PMID: 16473856, 17344927, 20301304, 21357940, 24319098). This variant is present in population databases (rs760094345, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with autosomal recessive junctional epidermolysis bullosa (PMID: 33274474). ClinVar contains an entry for this variant (Variation ID: 585309). For these reasons, this variant has been classified as Pathogenic. - |
Epidermolysis bullosa, junctional 4, intermediate Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at