rs4918079

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000494.4(COL17A1):c.2595C>T(p.Arg865Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,611,580 control chromosomes in the GnomAD database, including 524,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 41192 hom., cov: 32)

Exomes 𝑓: 0.81 ( 482885 hom. )

Consequence

COL17A1
NM_000494.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.211

Publications

26 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 10-104041495-G-A is Benign according to our data. Variant chr10-104041495-G-A is described in ClinVar as [Benign]. Clinvar id is 256269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.211 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL17A1	NM_000494.4 link	c.2595C>T	p.Arg865Arg	synonymous_variant	Exon 37 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.2595C>T	p.Arg865Arg	synonymous_variant	Exon 37 of 56		NM_000494.4	ENSP00000497653.1		Q9UMD9-1
COL17A1	ENST00000369733.8 link	c.2595C>T	p.Arg865Arg	synonymous_variant	Exon 36 of 51	5		ENSP00000358748.3		Q9UMD9-2

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109670

AN:

151710

Hom.:

41198

Cov.:

show subpopulations

Gnomad AFR

AF:

0.494

Gnomad AMI

AF:

0.878

Gnomad AMR

AF:

0.784

Gnomad ASJ

AF:

0.821

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.769

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.830

Gnomad OTH

AF:

0.751

GnomAD2 exomes

AF:

0.776

AC:

193833

AN:

249860

AF XY:

0.778

show subpopulations

Gnomad AFR exome

AF:

0.487

Gnomad AMR exome

AF:

0.783

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.788

Gnomad FIN exome

AF:

0.768

Gnomad NFE exome

AF:

0.828

Gnomad OTH exome

AF:

0.803

GnomAD4 exome

AF:

0.810

AC:

1183113

AN:

1459748

Hom.:

482885

Cov.:

AF XY:

0.808

AC XY:

587004

AN XY:

726238

show subpopulations

African (AFR)

AF:

0.476

AC:

15895

AN:

33396

American (AMR)

AF:

0.782

AC:

34898

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.803

AC:

20970

AN:

26106

East Asian (EAS)

AF:

0.749

AC:

29715

AN:

39686

South Asian (SAS)

AF:

0.714

AC:

61462

AN:

86136

European-Finnish (FIN)

AF:

0.771

AC:

41133

AN:

53384

Middle Eastern (MID)

AF:

0.774

AC:

4456

AN:

5758

European-Non Finnish (NFE)

AF:

0.835

AC:

926938

AN:

1110346

Other (OTH)

AF:

0.790

AC:

47646

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

10942

21885

32827

43770

54712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.722

AC:

109691

AN:

151832

Hom.:

41192

Cov.:

AF XY:

0.722

AC XY:

53572

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.494

AC:

20409

AN:

41320

American (AMR)

AF:

0.784

AC:

11977

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

2844

AN:

3466

East Asian (EAS)

AF:

0.775

AC:

3967

AN:

5116

South Asian (SAS)

AF:

0.697

AC:

3346

AN:

4802

European-Finnish (FIN)

AF:

0.769

AC:

8140

AN:

10584

Middle Eastern (MID)

AF:

0.796

AC:

234

AN:

294

European-Non Finnish (NFE)

AF:

0.830

AC:

56405

AN:

67946

Other (OTH)

AF:

0.745

AC:

1570

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1349

2699

4048

5398

6747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.784

Hom.:

39232

Bravo

AF:

0.716

Asia WGS

AF:

0.693

AC:

2405

AN:

3476

EpiCase

AF:

0.832

EpiControl

AF:

0.827

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) -

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

-0.44

CADD

Benign

0.93

(source)

DANN

Benign

0.63

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs4918079

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