10-104039458-G-T

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.2883C>A(p.Pro961Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,613,760 control chromosomes in the GnomAD database, including 530,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 41450 hom., cov: 32)

Exomes 𝑓: 0.81 ( 488715 hom. )

Consequence

COL17A1
NM_000494.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.03

Publications

24 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=-0.58).

BP6

Variant 10-104039458-G-T is Benign according to our data. Variant chr10-104039458-G-T is described in ClinVar as [Benign]. Clinvar id is 256270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.03 with no splicing effect.

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.2883C>A	p.Pro961Pro	synonymous_variant	Exon 43 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.2883C>A	p.Pro961Pro	synonymous_variant	Exon 43 of 56		NM_000494.4	ENSP00000497653.1		Q9UMD9-1
COL17A1	ENST00000369733.8 link	c.2762-337C>A		intron_variant	Intron 39 of 50	5		ENSP00000358748.3		Q9UMD9-2

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109796

AN:

151918

Hom.:

41455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.785

Gnomad ASJ

AF:

0.819

Gnomad EAS

AF:

0.842

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.752

GnomAD2 exomes

AF:

0.782

AC:

196671

AN:

251448

AF XY:

0.785

show subpopulations

Gnomad AFR exome

AF:

0.475

Gnomad AMR exome

AF:

0.786

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.856

Gnomad FIN exome

AF:

0.770

Gnomad NFE exome

AF:

0.830

Gnomad OTH exome

AF:

0.808

GnomAD4 exome

AF:

0.815

AC:

1191192

AN:

1461722

Hom.:

488715

Cov.:

AF XY:

0.813

AC XY:

590978

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.464

AC:

15541

AN:

33466

American (AMR)

AF:

0.785

AC:

35083

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.804

AC:

21005

AN:

26136

East Asian (EAS)

AF:

0.838

AC:

33283

AN:

39700

South Asian (SAS)

AF:

0.721

AC:

62155

AN:

86252

European-Finnish (FIN)

AF:

0.772

AC:

41256

AN:

53420

Middle Eastern (MID)

AF:

0.776

AC:

4447

AN:

5734

European-Non Finnish (NFE)

AF:

0.837

AC:

930442

AN:

1111906

Other (OTH)

AF:

0.795

AC:

47980

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

13370

26740

40110

53480

66850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.722

AC:

109811

AN:

152038

Hom.:

41450

Cov.:

AF XY:

0.722

AC XY:

53643

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.481

AC:

19913

AN:

41430

American (AMR)

AF:

0.784

AC:

11996

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.819

AC:

2841

AN:

3470

East Asian (EAS)

AF:

0.842

AC:

4350

AN:

5166

South Asian (SAS)

AF:

0.703

AC:

3385

AN:

4814

European-Finnish (FIN)

AF:

0.770

AC:

8151

AN:

10582

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.832

AC:

56571

AN:

67972

Other (OTH)

AF:

0.746

AC:

1571

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1397

2793

4190

5586

6983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.793

Hom.:

75287

Bravo

AF:

0.716

Asia WGS

AF:

0.716

AC:

2489

AN:

3478

EpiCase

AF:

0.834

EpiControl

AF:

0.829

ClinVar

Significance: Benign

Submissions summary: Benign:7

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

- -

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

-0.58

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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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10-104039458-G-T

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