rs17821926

Variant names:

• chr10-104055358-A-G
• rs17821926
• NM_000494.4:c.1717+14T>C

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.373
• Publications: 11 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000494.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL17A1	NM_000494.4	MANE Select	c.1717+14T>C		intron	N/A	NP_000485.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL17A1	ENST00000648076.2	MANE Select	c.1717+14T>C		intron	N/A	ENSP00000497653.1
	COL17A1	ENST00000480127.2	TSL:3	n.232T>C		non_coding_transcript_exon	Exon 2 of 2
	COL17A1	ENST00000369733.8	TSL:5	c.1717+14T>C		intron	N/A	ENSP00000358748.3

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

GnomAD2 exomes AF: 0.142 AC: 35691 AN: 251460 AF XY: 0.146

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 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

African (AFR) AF: 0.0306 AC: 1023 AN: 33480

American (AMR) AF: 0.150 AC: 6693 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5341 AN: 26128

East Asian (EAS) AF: 0.0480 AC: 1907 AN: 39700

South Asian (SAS) AF: 0.180 AC: 15504 AN: 86252

European-Finnish (FIN) AF: 0.0905 AC: 4833 AN: 53418

Middle Eastern (MID) AF: 0.194 AC: 1117 AN: 5766

European-Non Finnish (NFE) AF: 0.161 AC: 179476 AN: 1111896

Other (OTH) AF: 0.150 AC: 9030 AN: 60384

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

African (AFR) AF: 0.0356 AC: 1473 AN: 41376

American (AMR) AF: 0.159 AC: 2424 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3466

East Asian (EAS) AF: 0.0556 AC: 286 AN: 5142

South Asian (SAS) AF: 0.179 AC: 861 AN: 4806

European-Finnish (FIN) AF: 0.0787 AC: 826 AN: 10502

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11112 AN: 67922

Other (OTH) AF: 0.141 AC: 296 AN: 2096

Alfa AF: 0.156 Hom.: 3959

Bravo AF: 0.120

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Junctional epidermolysis bullosa, non-Herlitz type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17821926; hg19: chr10-105815116;