rs113786874

Variant names:

• chr10-104031871-CA-C
• rs113786874
• NM_000494.4:c.*363delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000494.4(COL17A1):​c.*363delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 319,058 control chromosomes in the GnomAD database, including 7,573 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4197 hom., cov: 27)
  • Exomes 𝑓: 0.19 (3376 hom.)
• Consequence: COL17A1 NM_000494.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-104031871-CA-C is Benign according to our data. Variant chr10-104031871-CA-C is described in ClinVar as [Benign]. Clinvar id is 298676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL17A1	NM_000494.4	c.*363delT		3_prime_UTR_variant	Exon 56 of 56	ENST00000648076.2	NP_000485.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2	c.*363delT		3_prime_UTR_variant	Exon 56 of 56		NM_000494.4	ENSP00000497653.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34366 AN: 151760 Hom.: 4177 Cov.: 27

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.192 AC: 32021 AN: 167180 Hom.: 3376 Cov.: 0 AF XY: 0.197 AC XY: 17381 AN XY: 88272

African (AFR) AF: 0.297 AC: 1733 AN: 5844

American (AMR) AF: 0.188 AC: 1422 AN: 7546

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 811 AN: 4846

East Asian (EAS) AF: 0.117 AC: 1135 AN: 9664

South Asian (SAS) AF: 0.258 AC: 5622 AN: 21754

European-Finnish (FIN) AF: 0.219 AC: 1565 AN: 7130

Middle Eastern (MID) AF: 0.195 AC: 138 AN: 706

European-Non Finnish (NFE) AF: 0.178 AC: 17846 AN: 100512

Other (OTH) AF: 0.191 AC: 1749 AN: 9178

GnomAD4 genome AF: 0.227 AC: 34448 AN: 151878 Hom.: 4197 Cov.: 27 AF XY: 0.228 AC XY: 16936 AN XY: 74210

African (AFR) AF: 0.311 AC: 12872 AN: 41406

American (AMR) AF: 0.186 AC: 2834 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3464

East Asian (EAS) AF: 0.127 AC: 656 AN: 5164

South Asian (SAS) AF: 0.281 AC: 1351 AN: 4808

European-Finnish (FIN) AF: 0.238 AC: 2498 AN: 10516

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12886 AN: 67938

Other (OTH) AF: 0.221 AC: 465 AN: 2108

Alfa AF: 0.0945 Hom.: 131

Bravo AF: 0.225

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Junctional epidermolysis bullosa Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs113786874; hg19: chr10-105791629;