chr10-104031871-CA-C

Position:

• chr10-104031871-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000494.4(COL17A1):​c.*363del 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
COL17A1	NM_000494.4	c.*363del		3_prime_UTR_variant	56/56	ENST00000648076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL17A1	ENST00000648076.2	c.*363del		3_prime_UTR_variant	56/56		NM_000494.4	A2
COL17A1	ENST00000369733.8	c.*363del		3_prime_UTR_variant	51/51	5		P4
COL17A1	ENST00000433822.1	c.*32-279del		intron_variant		5
COL17A1	ENST00000647647.1	c.*927del		3_prime_UTR_variant, NMD_transcript_variant	5/5

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

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.191

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

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.221

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs113786874; hg19: chr10-105791629;