10-104057158-C-T

Position:

chr10-104057158-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000494.4(COL17A1):c.1282G>A(p.Gly428Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 1,613,840 control chromosomes in the GnomAD database, including 755,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 58588 hom., cov: 32)

Exomes 𝑓: 0.97 ( 696735 hom. )

Consequence

COL17A1
NM_000494.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.699

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.6531384E-7).

BP6

Variant 10-104057158-C-T is Benign according to our data. Variant chr10-104057158-C-T is described in ClinVar as [Benign]. Clinvar id is 256266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104057158-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL17A1	NM_000494.4 linkuse as main transcript	c.1282G>A	p.Gly428Ser	missense_variant	17/56	ENST00000648076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL17A1	ENST00000648076.2 linkuse as main transcript	c.1282G>A	p.Gly428Ser	missense_variant	17/56		NM_000494.4	A2	Q9UMD9-1
COL17A1	ENST00000369733.8 linkuse as main transcript	c.1282G>A	p.Gly428Ser	missense_variant	16/51	5		P4	Q9UMD9-2
COL17A1	ENST00000650263.1 linkuse as main transcript	c.1234G>A	p.Gly412Ser	missense_variant	16/22

Frequencies

GnomAD3 genomes

AF:

0.857

AC:

130310

AN:

151994

Hom.:

58581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.998

Gnomad AMR

AF:

0.927

Gnomad ASJ

AF:

0.986

Gnomad EAS

AF:

0.884

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

0.944

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.994

Gnomad OTH

AF:

0.900

GnomAD3 exomes

AF:

0.940

AC:

233587

AN:

248608

Hom.:

111191

AF XY:

0.948

AC XY:

127838

AN XY:

134796

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.947

Gnomad ASJ exome

AF:

0.987

Gnomad EAS exome

AF:

0.888

Gnomad SAS exome

AF:

0.946

Gnomad FIN exome

AF:

0.944

Gnomad NFE exome

AF:

0.994

Gnomad OTH exome

AF:

0.956

GnomAD4 exome

AF:

0.974

AC:

1423027

AN:

1461728

Hom.:

696735

Cov.:

AF XY:

0.975

AC XY:

708647

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.535

Gnomad4 AMR exome

AF:

0.945

Gnomad4 ASJ exome

AF:

0.985

Gnomad4 EAS exome

AF:

0.866

Gnomad4 SAS exome

AF:

0.950

Gnomad4 FIN exome

AF:

0.946

Gnomad4 NFE exome

AF:

0.996

Gnomad4 OTH exome

AF:

0.946

GnomAD4 genome

AF:

0.857

AC:

130352

AN:

152112

Hom.:

58588

Cov.:

AF XY:

0.859

AC XY:

63857

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.554

Gnomad4 AMR

AF:

0.927

Gnomad4 ASJ

AF:

0.986

Gnomad4 EAS

AF:

0.884

Gnomad4 SAS

AF:

0.944

Gnomad4 FIN

AF:

0.944

Gnomad4 NFE

AF:

0.994

Gnomad4 OTH

AF:

0.901

Alfa

AF:

0.969

Hom.:

78770

Bravo

AF:

0.839

TwinsUK

AF:

0.994

AC:

3687

ALSPAC

AF:

0.996

AC:

3838

ESP6500AA

AF:

0.567

AC:

2498

ESP6500EA

AF:

0.993

AC:

8539

ExAC

AF:

0.934

AC:

113433

EpiCase

AF:

0.994

EpiControl

AF:

0.993

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 24668667) -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Epithelial recurrent erosion dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.1

DANN

Benign

0.72

DEOGEN2

Benign

0.12

.;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.41

T;.;T;T

MetaRNN

Benign

8.7e-7

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

N;N;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.030

N;N;.;.

REVEL

Benign

0.23

Sift

Benign

0.48

T;T;.;.

Sift4G

Benign

0.35

T;T;.;.

Polyphen

0.0010

B;B;B;.

Vest4

0.065

MPC

0.066

ClinPred

0.0089

GERP RS

1.7

Varity_R

0.019

gMVP

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over