chr10-104045739-C-T

Variant names:

• chr10-104045739-C-T
• rs813944
• NM_000494.4:c.2398+19G>A

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.2398+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,597,748 control chromosomes in the GnomAD database, including 213,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16096 hom., cov: 33)
  • Exomes 𝑓: 0.52 (197638 hom.)
• Consequence: COL17A1 NM_000494.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.535
• Publications: 6 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=-0.85).
• BP6: Variant 10-104045739-C-T is Benign according to our data. Variant chr10-104045739-C-T is described in ClinVar as Benign. ClinVar VariationId is 256268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 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.2398+19G>A		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.2398+19G>A		intron	N/A	ENSP00000497653.1
	COL17A1	ENST00000369733.8	TSL:5	c.2398+19G>A		intron	N/A	ENSP00000358748.3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66911 AN: 152078 Hom.: 16106 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.456

GnomAD2 exomes AF: 0.498 AC: 125171 AN: 251378 AF XY: 0.501

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.489

Gnomad EAS exome AF: 0.679

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.525

Gnomad OTH exome AF: 0.493

GnomAD4 exome AF: 0.519 AC: 750323 AN: 1445552 Hom.: 197638 Cov.: 31 AF XY: 0.518 AC XY: 373200 AN XY: 720156

African (AFR) AF: 0.220 AC: 7300 AN: 33246

American (AMR) AF: 0.469 AC: 20959 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 12711 AN: 26054

East Asian (EAS) AF: 0.679 AC: 26889 AN: 39610

South Asian (SAS) AF: 0.473 AC: 40647 AN: 85934

European-Finnish (FIN) AF: 0.488 AC: 26046 AN: 53356

Middle Eastern (MID) AF: 0.453 AC: 2595 AN: 5730

European-Non Finnish (NFE) AF: 0.531 AC: 582918 AN: 1097008

Other (OTH) AF: 0.505 AC: 30258 AN: 59906

GnomAD4 genome AF: 0.440 AC: 66895 AN: 152196 Hom.: 16096 Cov.: 33 AF XY: 0.439 AC XY: 32685 AN XY: 74432

African (AFR) AF: 0.239 AC: 9913 AN: 41518

American (AMR) AF: 0.448 AC: 6850 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1750 AN: 3472

East Asian (EAS) AF: 0.676 AC: 3502 AN: 5180

South Asian (SAS) AF: 0.450 AC: 2172 AN: 4824

European-Finnish (FIN) AF: 0.490 AC: 5198 AN: 10598

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35883 AN: 67998

Other (OTH) AF: 0.452 AC: 954 AN: 2112

Alfa AF: 0.489 Hom.: 30990

Bravo AF: 0.432

Asia WGS AF: 0.503 AC: 1746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Junctional epidermolysis bullosa, non-Herlitz type Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Epithelial recurrent erosion dystrophy Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.50
DANN	Benign	0.71
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs813944; hg19: chr10-105805497; COSMIC: COSV62230400; COSMIC: COSV62230400;