10-104037620-G-A

Variant names:

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

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

COL17A1 links:

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 ClinVar 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
COL17A1	NM_000494.4 link	c.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
COL17A1	ENST00000648076.2 link	c.3208+16C>T		intron_variant	Intron 46 of 55		NM_000494.4	ENSP00000497653.1		Q9UMD9-1
COL17A1	ENST00000369733.8 link	c.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.:

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.:

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

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

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.:

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

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

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

(source)

DANN

Benign

0.55

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over