Variant 10-104031858-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000494.4(COL17A1):c.*377G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000813 in 297,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 0 hom. )

Consequence

COL17A1
NM_000494.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0100

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL17A1	NM_000494.4 linkuse as main transcript	c.*377G>A		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.*377G>A	3_prime_UTR_variant	56/56		NM_000494.4	ENSP00000497653	A2	Q9UMD9-1
COL17A1	ENST00000369733.8 linkuse as main transcript	c.*377G>A	3_prime_UTR_variant	51/51	5		ENSP00000358748	P4	Q9UMD9-2
COL17A1	ENST00000433822.1 linkuse as main transcript	c.*32-265G>A	intron_variant		5		ENSP00000388832
COL17A1	ENST00000647647.1 linkuse as main transcript	c.*941G>A	3_prime_UTR_variant, NMD_transcript_variant	5/5			ENSP00000497865

Frequencies

GnomAD3 genomes

AF:

0.000952

AC:

137

AN:

143976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000543

Gnomad ASJ

AF:

0.00648

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000201

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000425

Gnomad OTH

AF:

0.00101

GnomAD4 exome

AF:

0.000684

AC:

105

AN:

153430

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

81220

show subpopulations

Gnomad4 AFR exome

AF:

0.000555

Gnomad4 AMR exome

AF:

0.000565

Gnomad4 ASJ exome

AF:

0.00422

Gnomad4 EAS exome

AF:

0.000115

Gnomad4 SAS exome

AF:

0.000238

Gnomad4 FIN exome

AF:

0.000160

Gnomad4 NFE exome

AF:

0.000686

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000951

AC:

137

AN:

144064

Hom.:

Cov.:

AF XY:

0.000925

AC XY:

AN XY:

70304

show subpopulations

Gnomad4 AFR

AF:

0.00199

Gnomad4 AMR

AF:

0.000542

Gnomad4 ASJ

AF:

0.00648

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000201

Gnomad4 NFE

AF:

0.000425

Gnomad4 OTH

AF:

0.00101

Alfa

AF:

0.000832

Hom.:

Bravo

AF:

0.000933

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Junctional epidermolysis bullosa, non-Herlitz type

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.9

DANN

Benign

0.65

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