rs805708

Positions:

chr10-104064575-G-A

Variant summary

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

The NM_000494.4(COL17A1):c.629C>T(p.Thr210Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.687 in 1,612,832 control chromosomes in the GnomAD database, including 386,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 29359 hom., cov: 31)

Exomes 𝑓: 0.70 ( 357168 hom. )

Consequence

COL17A1
NM_000494.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.27

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=5.8837804E-6).

BP6

Variant 10-104064575-G-A is Benign according to our data. Variant chr10-104064575-G-A is described in ClinVar as [Benign]. Clinvar id is 256276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104064575-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL17A1	NM_000494.4 linkuse as main transcript	c.629C>T	p.Thr210Met	missense_variant	10/56	ENST00000648076.2	NP_000485.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2 linkuse as main transcript	c.629C>T	p.Thr210Met	missense_variant	10/56		NM_000494.4	ENSP00000497653	A2	Q9UMD9-1

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91272

AN:

151980

Hom.:

29361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.698

Gnomad ASJ

AF:

0.696

Gnomad EAS

AF:

0.689

Gnomad SAS

AF:

0.632

Gnomad FIN

AF:

0.673

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.622

GnomAD3 exomes

AF:

0.676

AC:

168590

AN:

249226

Hom.:

58370

AF XY:

0.677

AC XY:

91205

AN XY:

134696

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.770

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.690

Gnomad SAS exome

AF:

0.636

Gnomad FIN exome

AF:

0.664

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.686

GnomAD4 exome

AF:

0.696

AC:

1016503

AN:

1460736

Hom.:

357168

Cov.:

AF XY:

0.695

AC XY:

504716

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.330

Gnomad4 AMR exome

AF:

0.760

Gnomad4 ASJ exome

AF:

0.688

Gnomad4 EAS exome

AF:

0.708

Gnomad4 SAS exome

AF:

0.637

Gnomad4 FIN exome

AF:

0.666

Gnomad4 NFE exome

AF:

0.712

Gnomad4 OTH exome

AF:

0.673

GnomAD4 genome

AF:

0.600

AC:

91284

AN:

152096

Hom.:

29359

Cov.:

AF XY:

0.602

AC XY:

44749

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.698

Gnomad4 ASJ

AF:

0.696

Gnomad4 EAS

AF:

0.689

Gnomad4 SAS

AF:

0.632

Gnomad4 FIN

AF:

0.673

Gnomad4 NFE

AF:

0.707

Gnomad4 OTH

AF:

0.615

Alfa

AF:

0.687

Hom.:

89996

Bravo

AF:

0.593

TwinsUK

AF:

0.712

AC:

2640

ALSPAC

AF:

0.714

AC:

2753

ESP6500AA

AF:

0.355

AC:

1564

ESP6500EA

AF:

0.703

AC:

6046

ExAC

AF:

0.666

AC:

80816

Asia WGS

AF:

0.569

AC:

1980

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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	- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -

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

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

.;D;D;.;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.74

T;.;T;T;T

MetaRNN

Benign

0.0000059

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.8

L;L;L;.;.

MutationTaster

Benign

0.62

P;P;P

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.7

D;D;.;.;D

REVEL

Benign

0.27

Sift

Benign

0.090

T;T;.;.;T

Sift4G

Pathogenic

0.0010

D;D;.;.;D

Polyphen

1.0

D;D;D;.;D

Vest4

0.76

MPC

0.068

ClinPred

0.045

GERP RS

5.6

Varity_R

0.11

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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