10-104036641-G-C

Variant names:

• chr10-104036641-G-C
• rs2274098
• NM_000494.4:c.3278-9C>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.3278-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,612,920 control chromosomes in the GnomAD database, including 532,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (42098 hom., cov: 33)
  • Exomes 𝑓: 0.82 (490540 hom.)
• Consequence: COL17A1 NM_000494.4 intron
• Scores: Splicing: ADA: 0.003205
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.655

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=-0.75).
• BP6: Variant 10-104036641-G-C is Benign according to our data. Variant chr10-104036641-G-C is described in ClinVar as [Benign]. Clinvar id is 256274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104036641-G-C 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 rank	MANE	Protein	UniProt
COL17A1	NM_000494.4	c.3278-9C>G		intron_variant	Intron 47 of 55	ENST00000648076.2	NP_000485.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2	c.3278-9C>G		intron_variant	Intron 47 of 55		NM_000494.4	ENSP00000497653.1
COL17A1	ENST00000369733.8	c.3143-9C>G		intron_variant	Intron 43 of 50	5		ENSP00000358748.3

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110985 AN: 151982 Hom.: 42104 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.757

GnomAD3 exomes AF: 0.786 AC: 195786 AN: 249126 Hom.: 78011 AF XY: 0.788 AC XY: 106271 AN XY: 134810

Gnomad AFR exome AF: 0.494

Gnomad AMR exome AF: 0.791

Gnomad ASJ exome AF: 0.820

Gnomad EAS exome AF: 0.855

Gnomad SAS exome AF: 0.726

Gnomad FIN exome AF: 0.769

Gnomad NFE exome AF: 0.830

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.817 AC: 1193492 AN: 1460820 Hom.: 490540 Cov.: 61 AF XY: 0.815 AC XY: 592261 AN XY: 726700

Gnomad4 AFR exome AF: 0.484

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.820

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.730

Gnomad4 FIN exome AF: 0.772

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.730 AC: 111006 AN: 152100 Hom.: 42098 Cov.: 33 AF XY: 0.729 AC XY: 54221 AN XY: 74346

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.751

Alfa AF: 0.803 Hom.: 15168

Bravo AF: 0.724

Asia WGS AF: 0.727 AC: 2525 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

- -

Junctional epidermolysis bullosa, non-Herlitz type Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.5
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0032
dbscSNV1_RF	Benign	0.056
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: rs2274098; hg19: chr10-105796399;