chr10-104036641-G-C
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000494.4(COL17A1):c.3278-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,612,920 control chromosomes in the GnomAD database, including 532,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.73 ( 42098 hom., cov: 33)
Exomes 𝑓: 0.82 ( 490540 hom. )
Consequence
COL17A1
NM_000494.4 splice_polypyrimidine_tract, intron
NM_000494.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.003205
2
Clinical Significance
Conservation
PhyloP100: 0.655
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 10-104036641-G-C is Benign according to our data. Variant chr10-104036641-G-C is described in ClinVar as [Benign]. Clinvar id is 256274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104036641-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL17A1 | NM_000494.4 | c.3278-9C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000648076.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL17A1 | ENST00000648076.2 | c.3278-9C>G | splice_polypyrimidine_tract_variant, intron_variant | NM_000494.4 | A2 | ||||
COL17A1 | ENST00000369733.8 | c.3143-9C>G | splice_polypyrimidine_tract_variant, intron_variant | 5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.730 AC: 110985AN: 151982Hom.: 42104 Cov.: 33
GnomAD3 genomes
AF:
AC:
110985
AN:
151982
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.786 AC: 195786AN: 249126Hom.: 78011 AF XY: 0.788 AC XY: 106271AN XY: 134810
GnomAD3 exomes
AF:
AC:
195786
AN:
249126
Hom.:
AF XY:
AC XY:
106271
AN XY:
134810
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.817 AC: 1193492AN: 1460820Hom.: 490540 Cov.: 61 AF XY: 0.815 AC XY: 592261AN XY: 726700
GnomAD4 exome
AF:
AC:
1193492
AN:
1460820
Hom.:
Cov.:
61
AF XY:
AC XY:
592261
AN XY:
726700
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.730 AC: 111006AN: 152100Hom.: 42098 Cov.: 33 AF XY: 0.729 AC XY: 54221AN XY: 74346
GnomAD4 genome
AF:
AC:
111006
AN:
152100
Hom.:
Cov.:
33
AF XY:
AC XY:
54221
AN XY:
74346
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2525
AN:
3478
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 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
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
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at