NM_000494.4:c.3208+16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000494.4(COL17A1):​c.3208+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,628 control chromosomes in the GnomAD database, including 531,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 41630 hom., cov: 32)
Exomes 𝑓: 0.82 ( 489634 hom. )

Consequence

COL17A1
NM_000494.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.972

Publications

11 publications found
Variant links:
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]
COL17A1 Gene-Disease associations (from GenCC):
  • epithelial recurrent erosion dystrophy
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia
  • epidermolysis bullosa, junctional 4, intermediate
    Inheritance: AR Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
  • junctional epidermolysis bullosa, non-Herlitz type
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)
  • amelogenesis imperfecta
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • generalized junctional epidermolysis bullosa non-Herlitz type
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • late-onset junctional epidermolysis bullosa
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • localized junctional epidermolysis bullosa, non-Herlitz type
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 10-104037620-G-A is Benign according to our data. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in CliVar as Benign. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
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 rank MANE Protein UniProt
COL17A1NM_000494.4 linkc.3208+16C>T intron_variant Intron 46 of 55 ENST00000648076.2 NP_000485.3 Q9UMD9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL17A1ENST00000648076.2 linkc.3208+16C>T intron_variant Intron 46 of 55 NM_000494.4 ENSP00000497653.1 Q9UMD9-1
COL17A1ENST00000369733.8 linkc.3073+16C>T intron_variant Intron 42 of 50 5 ENSP00000358748.3 Q9UMD9-2

Frequencies

GnomAD3 genomes
AF:
0.724
AC:
110057
AN:
151974
Hom.:
41637
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.482
Gnomad AMI
AF:
0.877
Gnomad AMR
AF:
0.793
Gnomad ASJ
AF:
0.830
Gnomad EAS
AF:
0.840
Gnomad SAS
AF:
0.704
Gnomad FIN
AF:
0.770
Gnomad MID
AF:
0.804
Gnomad NFE
AF:
0.833
Gnomad OTH
AF:
0.751
GnomAD2 exomes
AF:
0.784
AC:
197028
AN:
251384
AF XY:
0.786
show subpopulations
Gnomad AFR exome
AF:
0.476
Gnomad AMR exome
AF:
0.789
Gnomad ASJ exome
AF:
0.817
Gnomad EAS exome
AF:
0.855
Gnomad FIN exome
AF:
0.770
Gnomad NFE exome
AF:
0.830
Gnomad OTH exome
AF:
0.809
GnomAD4 exome
AF:
0.816
AC:
1192267
AN:
1461536
Hom.:
489634
Cov.:
51
AF XY:
0.814
AC XY:
591564
AN XY:
727074
show subpopulations
African (AFR)
AF:
0.465
AC:
15555
AN:
33468
American (AMR)
AF:
0.788
AC:
35263
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.817
AC:
21356
AN:
26130
East Asian (EAS)
AF:
0.839
AC:
33294
AN:
39700
South Asian (SAS)
AF:
0.724
AC:
62403
AN:
86238
European-Finnish (FIN)
AF:
0.772
AC:
41249
AN:
53402
Middle Eastern (MID)
AF:
0.777
AC:
4427
AN:
5694
European-Non Finnish (NFE)
AF:
0.837
AC:
930658
AN:
1111814
Other (OTH)
AF:
0.796
AC:
48062
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.471
Heterozygous variant carriers
0
12033
24066
36098
48131
60164
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
21010
42020
63030
84040
105050
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.724
AC:
110070
AN:
152092
Hom.:
41630
Cov.:
32
AF XY:
0.723
AC XY:
53781
AN XY:
74344
show subpopulations
African (AFR)
AF:
0.481
AC:
19958
AN:
41452
American (AMR)
AF:
0.793
AC:
12129
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.830
AC:
2880
AN:
3468
East Asian (EAS)
AF:
0.841
AC:
4334
AN:
5156
South Asian (SAS)
AF:
0.704
AC:
3393
AN:
4818
European-Finnish (FIN)
AF:
0.770
AC:
8152
AN:
10584
Middle Eastern (MID)
AF:
0.799
AC:
235
AN:
294
European-Non Finnish (NFE)
AF:
0.833
AC:
56615
AN:
68000
Other (OTH)
AF:
0.745
AC:
1574
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1369
2737
4106
5474
6843
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
826
1652
2478
3304
4130
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.792
Hom.:
136784
Bravo
AF:
0.717
Asia WGS
AF:
0.718
AC:
2494
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Junctional epidermolysis bullosa, non-Herlitz type Benign:1
Jul 22, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Epithelial recurrent erosion dystrophy Benign:1
Jul 22, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
1.0
DANN
Benign
0.55
PhyloP100
-0.97
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2282437; hg19: chr10-105797378; API