chr10-104036641-G-C

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.3278-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,612,920 control chromosomes in the GnomAD database, including 532,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 42098 hom., cov: 33)

Exomes 𝑓: 0.82 ( 490540 hom. )

Consequence

COL17A1
NM_000494.4 intron

Scores

Splicing: ADA: 0.003205

Clinical Significance

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

Conservation

PhyloP100: 0.655

Publications

12 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=-0.75).

BP6

Variant 10-104036641-G-C is Benign according to our data. Variant chr10-104036641-G-C is described in ClinVar as Benign. ClinVar VariationId is 256274.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.3278-9C>G		intron_variant	Intron 47 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.3278-9C>G		intron_variant	Intron 47 of 55		NM_000494.4	ENSP00000497653.1		Q9UMD9-1
COL17A1	ENST00000369733.8 link	c.3143-9C>G		intron_variant	Intron 43 of 50	5		ENSP00000358748.3		Q9UMD9-2

Frequencies

GnomAD3 genomes

AF:

0.730

AC:

110985

AN:

151982

Hom.:

42104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.878

Gnomad AMR

AF:

0.795

Gnomad ASJ

AF:

0.835

Gnomad EAS

AF:

0.840

Gnomad SAS

AF:

0.710

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.833

Gnomad OTH

AF:

0.757

GnomAD2 exomes

AF:

0.786

AC:

195786

AN:

249126

AF XY:

0.788

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.791

Gnomad ASJ exome

AF:

0.820

Gnomad EAS exome

AF:

0.855

Gnomad FIN exome

AF:

0.769

Gnomad NFE exome

AF:

0.830

Gnomad OTH exome

AF:

0.810

GnomAD4 exome

AF:

0.817

AC:

1193492

AN:

1460820

Hom.:

490540

Cov.:

AF XY:

0.815

AC XY:

592261

AN XY:

726700

show subpopulations

African (AFR)

AF:

0.484

AC:

16194

AN:

33466

American (AMR)

AF:

0.791

AC:

35278

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.820

AC:

21428

AN:

26124

East Asian (EAS)

AF:

0.839

AC:

33292

AN:

39690

South Asian (SAS)

AF:

0.730

AC:

62879

AN:

86180

European-Finnish (FIN)

AF:

0.772

AC:

41119

AN:

53232

Middle Eastern (MID)

AF:

0.778

AC:

4297

AN:

5526

European-Non Finnish (NFE)

AF:

0.837

AC:

930814

AN:

1111654

Other (OTH)

AF:

0.799

AC:

48191

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

12257

24515

36772

49030

61287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21020

42040

63060

84080

105100

<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:

0.730

AC:

111006

AN:

152100

Hom.:

42098

Cov.:

AF XY:

0.729

AC XY:

54221

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.501

AC:

20771

AN:

41456

American (AMR)

AF:

0.795

AC:

12158

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

2900

AN:

3472

East Asian (EAS)

AF:

0.841

AC:

4349

AN:

5174

South Asian (SAS)

AF:

0.710

AC:

3433

AN:

4832

European-Finnish (FIN)

AF:

0.770

AC:

8171

AN:

10608

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.833

AC:

56603

AN:

67942

Other (OTH)

AF:

0.751

AC:

1586

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1415

2830

4245

5660

7075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.803

Hom.:

15168

Bravo

AF:

0.724

Asia WGS

AF:

0.727

AC:

2525

AN:

3478

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

- -

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

- -

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

-0.75

CADD

Benign

8.5

(source)

DANN

Benign

0.64

PhyloP100

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0032

dbscSNV1_RF

Benign

0.056

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