rs11191910

Variant names:

• chr10-104058133-G-A
• rs11191910
• NM_000494.4:c.1267+13C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-104058133-G-A
• chr10-104058133-G-C
• chr10-104058133-G-T

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.1267+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,846 control chromosomes in the GnomAD database, including 23,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1795 hom., cov: 31)
  • Exomes 𝑓: 0.17 (22146 hom.)
• Consequence: COL17A1 NM_000494.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.09
• Publications: 10 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 (BayesDel_noAF=-0.91).
• BP6: Variant 10-104058133-G-A is Benign according to our data. Variant chr10-104058133-G-A is described in ClinVar as Benign. ClinVar VariationId is 256265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 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.1267+13C>T		intron	N/A	NP_000485.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL17A1	ENST00000648076.2	MANE Select	c.1267+13C>T		intron	N/A	ENSP00000497653.1	Q9UMD9-1
	COL17A1	ENST00000859462.1		c.1267+13C>T		intron	N/A	ENSP00000529521.1
	COL17A1	ENST00000859464.1		c.1264+13C>T		intron	N/A	ENSP00000529523.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21447 AN: 152098 Hom.: 1784 Cov.: 31

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.145

GnomAD2 exomes AF: 0.162 AC: 40756 AN: 251212 AF XY: 0.168

Gnomad AFR exome AF: 0.0563

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.221

Gnomad EAS exome AF: 0.103

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.171 AC: 250176 AN: 1461630 Hom.: 22146 Cov.: 33 AF XY: 0.173 AC XY: 125610 AN XY: 727106

African (AFR) AF: 0.0562 AC: 1881 AN: 33480

American (AMR) AF: 0.125 AC: 5578 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5711 AN: 26122

East Asian (EAS) AF: 0.0886 AC: 3516 AN: 39696

South Asian (SAS) AF: 0.190 AC: 16350 AN: 86232

European-Finnish (FIN) AF: 0.197 AC: 10540 AN: 53394

Middle Eastern (MID) AF: 0.168 AC: 966 AN: 5750

European-Non Finnish (NFE) AF: 0.176 AC: 195704 AN: 1111856

Other (OTH) AF: 0.164 AC: 9930 AN: 60386

GnomAD4 genome AF: 0.141 AC: 21471 AN: 152216 Hom.: 1795 Cov.: 31 AF XY: 0.143 AC XY: 10633 AN XY: 74424

African (AFR) AF: 0.0602 AC: 2501 AN: 41550

American (AMR) AF: 0.132 AC: 2025 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 719 AN: 3470

East Asian (EAS) AF: 0.0997 AC: 516 AN: 5176

South Asian (SAS) AF: 0.201 AC: 967 AN: 4818

European-Finnish (FIN) AF: 0.199 AC: 2106 AN: 10582

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12190 AN: 67998

Other (OTH) AF: 0.153 AC: 323 AN: 2116

Alfa AF: 0.162 Hom.: 2967

Bravo AF: 0.129

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Junctional epidermolysis bullosa, non-Herlitz type (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.42
PhyloP100		-2.1
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: rs11191910; hg19: chr10-105817891; COSMIC: COSV62226928; COSMIC: COSV62226928;