rs805722

Variant names:

• chr10-104050642-T-C
• rs805722
• NM_000494.4:c.2107A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-104050642-T-C
• chr10-104050642-T-A
• chr10-104050642-T-G

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.2107A>G​(p.Met703Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,613,354 control chromosomes in the GnomAD database, including 522,823 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41598 hom., cov: 31)
  • Exomes 𝑓: 0.81 (481225 hom.)
• Consequence: COL17A1 NM_000494.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.188
• Publications: 47 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: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.5010075E-6).
• BP6: Variant 10-104050642-T-C is Benign according to our data. Variant chr10-104050642-T-C is described in ClinVar as Benign. ClinVar VariationId is 256267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.815 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.2107A>G	p.Met703Val	missense	Exon 27 of 56	NP_000485.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL17A1	ENST00000648076.2	MANE Select	c.2107A>G	p.Met703Val	missense	Exon 27 of 56	ENSP00000497653.1	Q9UMD9-1
	COL17A1	ENST00000859462.1		c.2107A>G	p.Met703Val	missense	Exon 27 of 56	ENSP00000529521.1
	COL17A1	ENST00000859464.1		c.2104A>G	p.Met702Val	missense	Exon 27 of 56	ENSP00000529523.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110640 AN: 151924 Hom.: 41602 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.766

GnomAD2 exomes AF: 0.785 AC: 197385 AN: 251486 AF XY: 0.787

Gnomad AFR exome AF: 0.520

Gnomad AMR exome AF: 0.829

Gnomad ASJ exome AF: 0.803

Gnomad EAS exome AF: 0.789

Gnomad FIN exome AF: 0.745

Gnomad NFE exome AF: 0.822

Gnomad OTH exome AF: 0.796

GnomAD4 exome AF: 0.810 AC: 1182935 AN: 1461312 Hom.: 481225 Cov.: 100 AF XY: 0.809 AC XY: 587897 AN XY: 726988

African (AFR) AF: 0.507 AC: 16961 AN: 33472

American (AMR) AF: 0.825 AC: 36881 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 21073 AN: 26136

East Asian (EAS) AF: 0.780 AC: 30949 AN: 39700

South Asian (SAS) AF: 0.762 AC: 65722 AN: 86222

European-Finnish (FIN) AF: 0.751 AC: 40104 AN: 53418

Middle Eastern (MID) AF: 0.800 AC: 4237 AN: 5298

European-Non Finnish (NFE) AF: 0.827 AC: 919165 AN: 1111998

Other (OTH) AF: 0.793 AC: 47843 AN: 60344

GnomAD4 genome AF: 0.728 AC: 110662 AN: 152042 Hom.: 41598 Cov.: 31 AF XY: 0.727 AC XY: 53993 AN XY: 74304

African (AFR) AF: 0.521 AC: 21586 AN: 41398

American (AMR) AF: 0.799 AC: 12226 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2823 AN: 3470

East Asian (EAS) AF: 0.786 AC: 4059 AN: 5166

South Asian (SAS) AF: 0.742 AC: 3571 AN: 4814

European-Finnish (FIN) AF: 0.747 AC: 7913 AN: 10590

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55817 AN: 67992

Other (OTH) AF: 0.760 AC: 1603 AN: 2110

Alfa AF: 0.789 Hom.: 143575

Bravo AF: 0.724

TwinsUK AF: 0.832 AC: 3084

ALSPAC AF: 0.831 AC: 3204

ESP6500AA AF: 0.525 AC: 2313

ESP6500EA AF: 0.818 AC: 7039

ExAC AF: 0.780 AC: 94732

Asia WGS AF: 0.690 AC: 2400 AN: 3478

EpiCase AF: 0.826

EpiControl AF: 0.821

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Junctional epidermolysis bullosa, non-Herlitz type (2)
-	-	1	Epithelial recurrent erosion dystrophy (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	4.8
DANN	Benign	0.72
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0000075	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.080	N
PhyloP100		-0.19
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.22
Sift	Benign	0.56	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.077
MPC		0.067
ClinPred		0.0010	T
GERP RS		-4.2
Varity_R		0.049
gMVP		0.21
Mutation Taster		=88/12	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: rs805722; hg19: chr10-105810400; COSMIC: COSV62228414; COSMIC: COSV62228414;