rs805701

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.1062C>T(p.Ala354Ala) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.61

Publications

22 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=-0.49).

BP6

Variant 10-104060198-G-A is Benign according to our data. Variant chr10-104060198-G-A is described in ClinVar as Benign. ClinVar VariationId is 256263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL17A1	NM_000494.4 link	c.1062C>T	p.Ala354Ala	synonymous_variant	Exon 14 of 56	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.1062C>T	p.Ala354Ala	synonymous_variant	Exon 14 of 56		NM_000494.4	ENSP00000497653.1		Q9UMD9-1

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

87244

AN:

151906

Hom.:

27082

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.629

Gnomad FIN

AF:

0.666

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.678

Gnomad OTH

AF:

0.596

GnomAD2 exomes

AF:

0.657

AC:

165344

AN:

251492

AF XY:

0.659

show subpopulations

Gnomad AFR exome

AF:

0.310

Gnomad AMR exome

AF:

0.759

Gnomad ASJ exome

AF:

0.647

Gnomad EAS exome

AF:

0.695

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.678

Gnomad OTH exome

AF:

0.657

GnomAD4 exome

AF:

0.670

AC:

979289

AN:

1461870

Hom.:

331344

Cov.:

AF XY:

0.669

AC XY:

486699

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.300

AC:

10044

AN:

33480

American (AMR)

AF:

0.748

AC:

33464

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

17119

AN:

26136

East Asian (EAS)

AF:

0.709

AC:

28148

AN:

39700

South Asian (SAS)

AF:

0.634

AC:

54691

AN:

86254

European-Finnish (FIN)

AF:

0.658

AC:

35165

AN:

53416

Middle Eastern (MID)

AF:

0.622

AC:

3588

AN:

5766

European-Non Finnish (NFE)

AF:

0.682

AC:

758113

AN:

1112002

Other (OTH)

AF:

0.645

AC:

38957

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

22097

44194

66291

88388

110485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19368

38736

58104

77472

96840

<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:

0.574

AC:

87259

AN:

152024

Hom.:

27083

Cov.:

AF XY:

0.577

AC XY:

42877

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.309

AC:

12810

AN:

41430

American (AMR)

AF:

0.678

AC:

10364

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

2320

AN:

3468

East Asian (EAS)

AF:

0.694

AC:

3584

AN:

5166

South Asian (SAS)

AF:

0.630

AC:

3024

AN:

4802

European-Finnish (FIN)

AF:

0.666

AC:

7030

AN:

10556

Middle Eastern (MID)

AF:

0.582

AC:

170

AN:

292

European-Non Finnish (NFE)

AF:

0.678

AC:

46112

AN:

68004

Other (OTH)

AF:

0.590

AC:

1243

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1725

3450

5176

6901

8626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.635

Hom.:

90762

Bravo

AF:

0.564

Asia WGS

AF:

0.563

AC:

1958

AN:

3478

EpiCase

AF:

0.680

EpiControl

AF:

0.675

ClinVar

Significance: Benign

Submissions summary: Benign:7

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jul 22, 2021

Genome-Nilou Lab

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

- -

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

-0.49

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

4.6

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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