rs2282437

Variant names:

• chr10-104037620-G-A
• rs2282437
• NM_000494.4:c.3208+16C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-104037620-G-A
• chr10-104037620-G-C
• chr10-104037620-G-T

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.3208+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,628 control chromosomes in the GnomAD database, including 531,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (41630 hom., cov: 32)
  • Exomes 𝑓: 0.82 (489634 hom.)
• Consequence: COL17A1 NM_000494.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.972
• 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics, 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, PanelApp Australia
• 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=-0.87).
• BP6: Variant 10-104037620-G-A is Benign according to our data. Variant chr10-104037620-G-A is described in ClinVar as Benign. ClinVar VariationId is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL17A1	NM_000494.4	MANE Select	c.3208+16C>T		intron	N/A	NP_000485.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL17A1	ENST00000648076.2	MANE Select	c.3208+16C>T		intron	N/A	ENSP00000497653.1	Q9UMD9-1
	COL17A1	ENST00000859462.1		c.3208+16C>T		intron	N/A	ENSP00000529521.1
	COL17A1	ENST00000859464.1		c.3205+16C>T		intron	N/A	ENSP00000529523.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110057 AN: 151974 Hom.: 41637 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.751

GnomAD2 exomes AF: 0.784 AC: 197028 AN: 251384 AF XY: 0.786

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.789

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.855

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.830

Gnomad OTH exome AF: 0.809

GnomAD4 exome AF: 0.816 AC: 1192267 AN: 1461536 Hom.: 489634 Cov.: 51 AF XY: 0.814 AC XY: 591564 AN XY: 727074

African (AFR) AF: 0.465 AC: 15555 AN: 33468

American (AMR) AF: 0.788 AC: 35263 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 21356 AN: 26130

East Asian (EAS) AF: 0.839 AC: 33294 AN: 39700

South Asian (SAS) AF: 0.724 AC: 62403 AN: 86238

European-Finnish (FIN) AF: 0.772 AC: 41249 AN: 53402

Middle Eastern (MID) AF: 0.777 AC: 4427 AN: 5694

European-Non Finnish (NFE) AF: 0.837 AC: 930658 AN: 1111814

Other (OTH) AF: 0.796 AC: 48062 AN: 60368

GnomAD4 genome AF: 0.724 AC: 110070 AN: 152092 Hom.: 41630 Cov.: 32 AF XY: 0.723 AC XY: 53781 AN XY: 74344

African (AFR) AF: 0.481 AC: 19958 AN: 41452

American (AMR) AF: 0.793 AC: 12129 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2880 AN: 3468

East Asian (EAS) AF: 0.841 AC: 4334 AN: 5156

South Asian (SAS) AF: 0.704 AC: 3393 AN: 4818

European-Finnish (FIN) AF: 0.770 AC: 8152 AN: 10584

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56615 AN: 68000

Other (OTH) AF: 0.745 AC: 1574 AN: 2112

Alfa AF: 0.792 Hom.: 136784

Bravo AF: 0.717

Asia WGS AF: 0.718 AC: 2494 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Epithelial recurrent erosion dystrophy (1)
-	-	1	Junctional epidermolysis bullosa, non-Herlitz type (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2282437; hg19: chr10-105797378;