10-104045739-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.2398+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,597,748 control chromosomes in the GnomAD database, including 213,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16096 hom., cov: 33)

Exomes 𝑓: 0.52 ( 197638 hom. )

Consequence

COL17A1
NM_000494.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.535

Publications

6 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=-0.85).

BP6

Variant 10-104045739-C-T is Benign according to our data. Variant chr10-104045739-C-T is described in ClinVar as Benign. ClinVar VariationId is 256268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL17A1	NM_000494.4 link	c.2398+19G>A		intron_variant	Intron 33 of 55	ENST00000648076.2	NP_000485.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2 link	c.2398+19G>A		intron_variant	Intron 33 of 55		NM_000494.4	ENSP00000497653.1
COL17A1	ENST00000369733.8 link	c.2398+19G>A		intron_variant	Intron 32 of 50	5		ENSP00000358748.3

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66911

AN:

152078

Hom.:

16106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.580

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.456

GnomAD2 exomes

AF:

0.498

AC:

125171

AN:

251378

AF XY:

0.501

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.489

Gnomad EAS exome

AF:

0.679

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.493

GnomAD4 exome

AF:

0.519

AC:

750323

AN:

1445552

Hom.:

197638

Cov.:

AF XY:

0.518

AC XY:

373200

AN XY:

720156

show subpopulations

African (AFR)

AF:

0.220

AC:

7300

AN:

33246

American (AMR)

AF:

0.469

AC:

20959

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

12711

AN:

26054

East Asian (EAS)

AF:

0.679

AC:

26889

AN:

39610

South Asian (SAS)

AF:

0.473

AC:

40647

AN:

85934

European-Finnish (FIN)

AF:

0.488

AC:

26046

AN:

53356

Middle Eastern (MID)

AF:

0.453

AC:

2595

AN:

5730

European-Non Finnish (NFE)

AF:

0.531

AC:

582918

AN:

1097008

Other (OTH)

AF:

0.505

AC:

30258

AN:

59906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

16921

33842

50762

67683

84604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16512

33024

49536

66048

82560

<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:

0.440

AC:

66895

AN:

152196

Hom.:

16096

Cov.:

AF XY:

0.439

AC XY:

32685

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.239

AC:

9913

AN:

41518

American (AMR)

AF:

0.448

AC:

6850

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1750

AN:

3472

East Asian (EAS)

AF:

0.676

AC:

3502

AN:

5180

South Asian (SAS)

AF:

0.450

AC:

2172

AN:

4824

European-Finnish (FIN)

AF:

0.490

AC:

5198

AN:

10598

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.528

AC:

35883

AN:

67998

Other (OTH)

AF:

0.452

AC:

954

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1836

3672

5507

7343

9179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<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:

0.489

Hom.:

30990

Bravo

AF:

0.432

Asia WGS

AF:

0.503

AC:

1746

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

-0.85

CADD

Benign

0.50

(source)

DANN

Benign

0.71

PhyloP100

-0.54

Mutation Taster

=100/0

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