rs2282437

Positions:

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

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.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

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=-0.87).
• BP6: Variant 10-104037620-G-A is Benign according to our data. Variant chr10-104037620-G-A is described in ClinVar as [Benign]. Clinvar id is 256272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104037620-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL17A1	NM_000494.4	c.3208+16C>T		intron_variant		ENST00000648076.2	NP_000485.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2	c.3208+16C>T		intron_variant			NM_000494.4	ENSP00000497653.1
COL17A1	ENST00000369733.8	c.3073+16C>T		intron_variant		5		ENSP00000358748.3

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

GnomAD3 exomes AF: 0.784 AC: 197028 AN: 251384 Hom.: 78425 AF XY: 0.786 AC XY: 106844 AN XY: 135876

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 SAS exome AF: 0.720

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

Gnomad4 AFR exome AF: 0.465

Gnomad4 AMR exome AF: 0.788

Gnomad4 ASJ exome AF: 0.817

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.724

Gnomad4 FIN exome AF: 0.772

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 0.796

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

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.745

Alfa AF: 0.816 Hom.: 86844

Bravo AF: 0.717

Asia WGS AF: 0.718 AC: 2494 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Junctional epidermolysis bullosa, non-Herlitz type Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Epithelial recurrent erosion dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs2282437; hg19: chr10-105797378;