10-104057158-C-T

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.1282G>A(p.Gly428Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 1,613,840 control chromosomes in the GnomAD database, including 755,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 58588 hom., cov: 32)

Exomes 𝑓: 0.97 ( 696735 hom. )

Consequence

COL17A1
NM_000494.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.699

Publications

38 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 (MetaRNN=8.6531384E-7).

BP6

Variant 10-104057158-C-T is Benign according to our data. Variant chr10-104057158-C-T is described in ClinVar as Benign. ClinVar VariationId is 256266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000494.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL17A1	NM_000494.4	MANE Select	c.1282G>A	p.Gly428Ser	missense	Exon 17 of 56	NP_000485.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL17A1	ENST00000648076.2	MANE Select	c.1282G>A	p.Gly428Ser	missense	Exon 17 of 56	ENSP00000497653.1
COL17A1	ENST00000369733.8	TSL:5	c.1282G>A	p.Gly428Ser	missense	Exon 16 of 51	ENSP00000358748.3
COL17A1	ENST00000650263.1		c.1234G>A	p.Gly412Ser	missense	Exon 16 of 22	ENSP00000497850.1

Frequencies

GnomAD3 genomes

AF:

0.857

AC:

130310

AN:

151994

Hom.:

58581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.998

Gnomad AMR

AF:

0.927

Gnomad ASJ

AF:

0.986

Gnomad EAS

AF:

0.884

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

0.944

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.994

Gnomad OTH

AF:

0.900

GnomAD2 exomes

AF:

0.940

AC:

233587

AN:

248608

AF XY:

0.948

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.947

Gnomad ASJ exome

AF:

0.987

Gnomad EAS exome

AF:

0.888

Gnomad FIN exome

AF:

0.944

Gnomad NFE exome

AF:

0.994

Gnomad OTH exome

AF:

0.956

GnomAD4 exome

AF:

0.974

AC:

1423027

AN:

1461728

Hom.:

696735

Cov.:

AF XY:

0.975

AC XY:

708647

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.535

AC:

17903

AN:

33468

American (AMR)

AF:

0.945

AC:

42278

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.985

AC:

25746

AN:

26128

East Asian (EAS)

AF:

0.866

AC:

34382

AN:

39694

South Asian (SAS)

AF:

0.950

AC:

81940

AN:

86256

European-Finnish (FIN)

AF:

0.946

AC:

50524

AN:

53416

Middle Eastern (MID)

AF:

0.955

AC:

5498

AN:

5758

European-Non Finnish (NFE)

AF:

0.996

AC:

1107643

AN:

1111904

Other (OTH)

AF:

0.946

AC:

57113

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1835

3671

5506

7342

9177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21598

43196

64794

86392

107990

<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:

0.857

AC:

130352

AN:

152112

Hom.:

58588

Cov.:

AF XY:

0.859

AC XY:

63857

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.554

AC:

22932

AN:

41426

American (AMR)

AF:

0.927

AC:

14181

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.986

AC:

3422

AN:

3472

East Asian (EAS)

AF:

0.884

AC:

4549

AN:

5144

South Asian (SAS)

AF:

0.944

AC:

4554

AN:

4824

European-Finnish (FIN)

AF:

0.944

AC:

10019

AN:

10608

Middle Eastern (MID)

AF:

0.929

AC:

273

AN:

294

European-Non Finnish (NFE)

AF:

0.994

AC:

67610

AN:

68020

Other (OTH)

AF:

0.901

AC:

1902

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

600

1201

1801

2402

3002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.945

Hom.:

196028

Bravo

AF:

0.839

TwinsUK

AF:

0.994

AC:

3687

ALSPAC

AF:

0.996

AC:

3838

ESP6500AA

AF:

0.567

AC:

2498

ESP6500EA

AF:

0.993

AC:

8539

ExAC

AF:

0.934

AC:

113433

EpiCase

AF:

0.994

EpiControl

AF:

0.993

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

This variant is associated with the following publications: (PMID: 24668667)

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

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.1

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.12

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.41

MetaRNN

Benign

8.7e-7

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

PhyloP100

0.70

PrimateAI

Benign

0.31

PROVEAN

Benign

0.030

REVEL

Benign

0.23

Sift

Benign

0.48

Sift4G

Benign

0.35

Polyphen

0.0010

Vest4

0.065

MPC

0.066

ClinPred

0.0089

GERP RS

1.7

Varity_R

0.019

gMVP

0.20

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over