rs4918079

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000494.4(COL17A1):c.2595C>T(p.Arg865=) 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

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 -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. Variant chr10-104041495-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
COL17A1	NM_000494.4 linkuse as main transcript	c.2595C>T	p.Arg865=	synonymous_variant	37/56	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.2595C>T	p.Arg865=	synonymous_variant	37/56		NM_000494.4	ENSP00000497653	A2	Q9UMD9-1
COL17A1	ENST00000369733.8 linkuse as main transcript	c.2595C>T	p.Arg865=	synonymous_variant	36/51	5		ENSP00000358748	P4	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

GnomAD3 exomes

AF:

0.776

AC:

193833

AN:

249860

Hom.:

76270

AF XY:

0.778

AC XY:

105251

AN XY:

135342

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 SAS exome

AF:

0.709

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

Gnomad4 AFR exome

AF:

0.476

Gnomad4 AMR exome

AF:

0.782

Gnomad4 ASJ exome

AF:

0.803

Gnomad4 EAS exome

AF:

0.749

Gnomad4 SAS exome

AF:

0.714

Gnomad4 FIN exome

AF:

0.771

Gnomad4 NFE exome

AF:

0.835

Gnomad4 OTH exome

AF:

0.790

GnomAD4 genome

AF:

0.722

AC:

109691

AN:

151832

Hom.:

41192

Cov.:

AF XY:

0.722

AC XY:

53572

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.494

Gnomad4 AMR

AF:

0.784

Gnomad4 ASJ

AF:

0.821

Gnomad4 EAS

AF:

0.775

Gnomad4 SAS

AF:

0.697

Gnomad4 FIN

AF:

0.769

Gnomad4 NFE

AF:

0.830

Gnomad4 OTH

AF:

0.745

Alfa

AF:

0.786

Hom.:

29173

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 24668667) -
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 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. -

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

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.93

DANN

Benign

0.63

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

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