10-104086316-A-G

Variant names:

• chr10-104086316-A-G
• rs1320448
• ENST00000750777.1:n.194+18576A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000750777.1(ENSG00000297750):​n.194+18576A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,172 control chromosomes in the GnomAD database, including 65,033 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (65033 hom., cov: 29)
• Consequence: ENSG00000297750 ENST00000750777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 20 publications found

Genes affected

ENSG00000297750 (HGNC:):

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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• epidermolysis bullosa, junctional 4, intermediate

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, G2P
• junctional epidermolysis bullosa, non-Herlitz type

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000750777.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000297750	ENST00000750777.1		n.194+18576A>G		intron	N/A
	ENSG00000297750	ENST00000750778.1		n.68+3261A>G		intron	N/A
	COL17A1	ENST00000859462.1		c.-180T>C		upstream_gene	N/A	ENSP00000529521.1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139852 AN: 152054 Hom.: 65000 Cov.: 29

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.944

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.920 AC: 139942 AN: 152172 Hom.: 65033 Cov.: 29 AF XY: 0.919 AC XY: 68390 AN XY: 74394

African (AFR) AF: 0.768 AC: 31842 AN: 41466

American (AMR) AF: 0.951 AC: 14532 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3430 AN: 3468

East Asian (EAS) AF: 0.887 AC: 4570 AN: 5150

South Asian (SAS) AF: 0.952 AC: 4595 AN: 4826

European-Finnish (FIN) AF: 0.944 AC: 10024 AN: 10614

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67761 AN: 68038

Other (OTH) AF: 0.944 AC: 1998 AN: 2116

Alfa AF: 0.970 Hom.: 238680

Bravo AF: 0.912

Asia WGS AF: 0.893 AC: 3104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.60
PhyloP100		0.0090
PromoterAI		-0.016	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1320448; hg19: chr10-105846074;