NM_000494.4:c.3261T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000494.4(COL17A1):c.3261T>C(p.Ile1087Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,606,934 control chromosomes in the GnomAD database, including 799,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74291 hom., cov: 30)

Exomes 𝑓: 1.0 ( 725517 hom. )

Consequence

COL17A1
NM_000494.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.36

Publications

16 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 10-104037061-A-G is Benign according to our data. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037061-A-G is described in CliVar as Benign. Clinvar id is 256273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL17A1	NM_000494.4 link	c.3261T>C	p.Ile1087Ile	synonymous_variant	Exon 47 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.3261T>C	p.Ile1087Ile	synonymous_variant	Exon 47 of 56		NM_000494.4	ENSP00000497653.1		Q9UMD9-1
COL17A1	ENST00000369733.8 link	c.3126T>C	p.Ile1042Ile	synonymous_variant	Exon 43 of 51	5		ENSP00000358748.3		Q9UMD9-2

Frequencies

GnomAD3 genomes

AF:

0.988

AC:

150255

AN:

152092

Hom.:

74238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.957

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.996

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.994

GnomAD2 exomes

AF:

0.997

AC:

241513

AN:

242212

AF XY:

0.998

show subpopulations

Gnomad AFR exome

AF:

0.957

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.999

AC:

1452833

AN:

1454724

Hom.:

725517

Cov.:

AF XY:

0.999

AC XY:

722000

AN XY:

722766

show subpopulations

African (AFR)

AF:

0.951

AC:

31757

AN:

33376

American (AMR)

AF:

0.998

AC:

43893

AN:

43962

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

25988

AN:

25988

East Asian (EAS)

AF:

1.00

AC:

39630

AN:

39630

South Asian (SAS)

AF:

1.00

AC:

84533

AN:

84542

European-Finnish (FIN)

AF:

1.00

AC:

52956

AN:

52956

Middle Eastern (MID)

AF:

0.999

AC:

4585

AN:

4588

European-Non Finnish (NFE)

AF:

1.00

AC:

1109520

AN:

1109562

Other (OTH)

AF:

0.998

AC:

59971

AN:

60120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

105

210

316

421

526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21632

43264

64896

86528

108160

<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:

0.988

AC:

150368

AN:

152210

Hom.:

74291

Cov.:

AF XY:

0.988

AC XY:

73548

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.957

AC:

39745

AN:

41514

American (AMR)

AF:

0.996

AC:

15241

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5154

AN:

5154

South Asian (SAS)

AF:

1.00

AC:

4822

AN:

4822

European-Finnish (FIN)

AF:

1.00

AC:

10600

AN:

10600

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68033

AN:

68038

Other (OTH)

AF:

0.994

AC:

2095

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

175

263

350

438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.995

Hom.:

33413

Bravo

AF:

0.987

Asia WGS

AF:

0.999

AC:

3473

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

- -

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

-0.51

CADD

Benign

9.3

(source)

DANN

Benign

0.74

PhyloP100

1.4

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