rs17821926

chr10-104055358-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000494.4(COL17A1):c.1717+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,613,480 control chromosomes in the GnomAD database, including 19,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1443 hom., cov: 30)
  • Exomes 𝑓: 0.15 (18496 hom.)
• Consequence: COL17A1 NM_000494.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.373

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-104055358-A-G is Benign according to our data. Variant chr10-104055358-A-G is described in ClinVar as [Benign]. Clinvar id is 298725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL17A1	NM_000494.4	c.1717+14T>C		intron_variant		ENST00000648076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL17A1	ENST00000648076.2	c.1717+14T>C		intron_variant			NM_000494.4	A2
COL17A1	ENST00000369733.8	c.1717+14T>C		intron_variant		5		P4
COL17A1	ENST00000650263.1	c.1669+14T>C		intron_variant
COL17A1	ENST00000480127.2	n.232T>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18148 AN: 151618 Hom.: 1438 Cov.: 30

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.142 AC: 35691 AN: 251460 Hom.: 2857 AF XY: 0.146 AC XY: 19891 AN XY: 135910

Gnomad AFR exome AF: 0.0343

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.0632

Gnomad SAS exome AF: 0.179

Gnomad FIN exome AF: 0.0867

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.154 AC: 224924 AN: 1461744 Hom.: 18496 Cov.: 41 AF XY: 0.155 AC XY: 113037 AN XY: 727190

Gnomad4 AFR exome AF: 0.0306

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.0480

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.0905

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.120 AC: 18163 AN: 151736 Hom.: 1443 Cov.: 30 AF XY: 0.118 AC XY: 8719 AN XY: 74110

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0556

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0787

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.141

Alfa AF: 0.161 Hom.: 3084

Bravo AF: 0.120

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Junctional epidermolysis bullosa, non-Herlitz type Benign:1

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 provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs17821926; hg19: chr10-105815116;