10-104032227-T-C

Position:

chr10-104032227-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000494.4(COL17A1):c.*8A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000277 in 1,612,218 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

COL17A1
NM_000494.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.680

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-104032227-T-C is Benign according to our data. Variant chr10-104032227-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 298680.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00149 (227/152334) while in subpopulation AFR AF= 0.00527 (219/41580). AF 95% confidence interval is 0.0047. There are 2 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL17A1	NM_000494.4 linkuse as main transcript	c.*8A>G		3_prime_UTR_variant	56/56	ENST00000648076.2	NP_000485.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2 linkuse as main transcript	c.*8A>G	3_prime_UTR_variant	56/56		NM_000494.4	ENSP00000497653	A2	Q9UMD9-1
COL17A1	ENST00000369733.8 linkuse as main transcript	c.*8A>G	3_prime_UTR_variant	51/51	5		ENSP00000358748	P4	Q9UMD9-2
COL17A1	ENST00000433822.1 linkuse as main transcript	c.*8A>G	3_prime_UTR_variant	3/4	5		ENSP00000388832
COL17A1	ENST00000647647.1 linkuse as main transcript	c.*572A>G	3_prime_UTR_variant, NMD_transcript_variant	5/5			ENSP00000497865

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

226

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00526

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251386

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00517

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000150

AC:

219

AN:

1459884

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

726326

show subpopulations

Gnomad4 AFR exome

AF:

0.00556

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.00149

AC:

227

AN:

152334

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00527

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.00166

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

COL17A1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

DANN

Benign

0.44

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over