rs805701
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000494.4(COL17A1):c.1062C>T(p.Ala354=) variant causes a synonymous change. The variant allele was found at a frequency of 0.661 in 1,613,894 control chromosomes in the GnomAD database, including 358,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.57 ( 27083 hom., cov: 31)
Exomes 𝑓: 0.67 ( 331344 hom. )
Consequence
COL17A1
NM_000494.4 synonymous
NM_000494.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.61
Genes affected
COL17A1 (HGNC:2194): (collagen type XVII alpha 1 chain) This gene encodes the alpha chain of type XVII collagen. Unlike most collagens, collagen XVII is a transmembrane protein. Collagen XVII is a structural component of hemidesmosomes, multiprotein complexes at the dermal-epidermal basement membrane zone that mediate adhesion of keratinocytes to the underlying membrane. Mutations in this gene are associated with both generalized atrophic benign and junctional epidermolysis bullosa. Two homotrimeric forms of type XVII collagen exist. The full length form is the transmembrane protein. A soluble form, referred to as either ectodomain or LAD-1, is generated by proteolytic processing of the full length form. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 10-104060198-G-A is Benign according to our data. Variant chr10-104060198-G-A is described in ClinVar as [Benign]. Clinvar id is 256263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104060198-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL17A1 | NM_000494.4 | c.1062C>T | p.Ala354= | synonymous_variant | 14/56 | ENST00000648076.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL17A1 | ENST00000648076.2 | c.1062C>T | p.Ala354= | synonymous_variant | 14/56 | NM_000494.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.574 AC: 87244AN: 151906Hom.: 27082 Cov.: 31
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GnomAD3 exomes AF: 0.657 AC: 165344AN: 251492Hom.: 55822 AF XY: 0.659 AC XY: 89546AN XY: 135920
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GnomAD4 exome AF: 0.670 AC: 979289AN: 1461870Hom.: 331344 Cov.: 87 AF XY: 0.669 AC XY: 486699AN XY: 727234
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GnomAD4 genome AF: 0.574 AC: 87259AN: 152024Hom.: 27083 Cov.: 31 AF XY: 0.577 AC XY: 42877AN XY: 74276
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Junctional epidermolysis bullosa, non-Herlitz type Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Epithelial recurrent erosion dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at