rs17116471

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.10A>G(p.Thr4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00763 in 1,613,286 control chromosomes in the GnomAD database, including 1,179 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T4I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.010 ( 96 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 1083 hom. )

Consequence

COL17A1
NM_000494.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.45

Publications

15 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:

ENSG00000297750 (HGNC:):

ENSG00000297750 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=0.001486063).

BP6

Variant 10-104080664-T-C is Benign according to our data. Variant chr10-104080664-T-C is described in ClinVar as [Benign]. Clinvar id is 256264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL17A1	NM_000494.4 link	c.10A>G	p.Thr4Ala	missense_variant	Exon 2 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.10A>G	p.Thr4Ala	missense_variant	Exon 2 of 56		NM_000494.4	ENSP00000497653.1		Q9UMD9-1

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1528

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0728

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0455

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.0328

AC:

8227

AN:

250840

AF XY:

0.0252

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0416

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.0201

GnomAD4 exome

AF:

0.00738

AC:

10778

AN:

1460958

Hom.:

1083

Cov.:

AF XY:

0.00633

AC XY:

4599

AN XY:

726780

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

33470

American (AMR)

AF:

0.193

AC:

8613

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0390

AC:

1548

AN:

39652

South Asian (SAS)

AF:

0.000719

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52656

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000167

AC:

186

AN:

1111948

Other (OTH)

AF:

0.00523

AC:

316

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

489

978

1467

1956

2445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0100

AC:

1529

AN:

152328

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

781

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00294

AC:

122

AN:

41556

American (AMR)

AF:

0.0729

AC:

1115

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0455

AC:

236

AN:

5192

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68028

Other (OTH)

AF:

0.00992

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

138

208

277

346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00844

Hom.:

216

Bravo

AF:

0.0202

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0256

AC:

3108

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 02, 2021

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

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

.;T;T;.;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.64

T;.;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L;.;.

PhyloP100

3.5

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.0

N;N;.;.;D

REVEL

Benign

0.076

Sift

Uncertain

0.0030

D;D;.;.;D

Sift4G

Benign

0.12

T;T;.;.;T

Polyphen

0.57

P;P;P;.;P

Vest4

0.097

MPC

0.065

ClinPred

0.026

GERP RS

5.2

PromoterAI

0.031

Neutral

(source)

Varity_R

0.13

gMVP

0.25

Mutation Taster

=90/10

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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rs17116471

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