chr10-104039458-G-T

Position:

chr10-104039458-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000494.4(COL17A1):c.2883C>A(p.Pro961=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,613,760 control chromosomes in the GnomAD database, including 530,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 41450 hom., cov: 32)

Exomes 𝑓: 0.81 ( 488715 hom. )

Consequence

COL17A1
NM_000494.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.03

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 10-104039458-G-T is Benign according to our data. Variant chr10-104039458-G-T is described in ClinVar as [Benign]. Clinvar id is 256270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-104039458-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL17A1	NM_000494.4 linkuse as main transcript	c.2883C>A	p.Pro961=	synonymous_variant	43/56	ENST00000648076.2	NP_000485.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2 linkuse as main transcript	c.2883C>A	p.Pro961=	synonymous_variant	43/56		NM_000494.4	ENSP00000497653	A2	Q9UMD9-1
COL17A1	ENST00000369733.8 linkuse as main transcript	c.2762-337C>A		intron_variant		5		ENSP00000358748	P4	Q9UMD9-2

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109796

AN:

151918

Hom.:

41455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.785

Gnomad ASJ

AF:

0.819

Gnomad EAS

AF:

0.842

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.752

GnomAD3 exomes

AF:

0.782

AC:

196671

AN:

251448

Hom.:

78118

AF XY:

0.785

AC XY:

106641

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.475

Gnomad AMR exome

AF:

0.786

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.856

Gnomad SAS exome

AF:

0.717

Gnomad FIN exome

AF:

0.770

Gnomad NFE exome

AF:

0.830

Gnomad OTH exome

AF:

0.808

GnomAD4 exome

AF:

0.815

AC:

1191192

AN:

1461722

Hom.:

488715

Cov.:

AF XY:

0.813

AC XY:

590978

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.785

Gnomad4 ASJ exome

AF:

0.804

Gnomad4 EAS exome

AF:

0.838

Gnomad4 SAS exome

AF:

0.721

Gnomad4 FIN exome

AF:

0.772

Gnomad4 NFE exome

AF:

0.837

Gnomad4 OTH exome

AF:

0.795

GnomAD4 genome

AF:

0.722

AC:

109811

AN:

152038

Hom.:

41450

Cov.:

AF XY:

0.722

AC XY:

53643

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.481

Gnomad4 AMR

AF:

0.784

Gnomad4 ASJ

AF:

0.819

Gnomad4 EAS

AF:

0.842

Gnomad4 SAS

AF:

0.703

Gnomad4 FIN

AF:

0.770

Gnomad4 NFE

AF:

0.832

Gnomad4 OTH

AF:

0.746

Alfa

AF:

0.805

Hom.:

62211

Bravo

AF:

0.716

Asia WGS

AF:

0.716

AC:

2489

AN:

3478

EpiCase

AF:

0.834

EpiControl

AF:

0.829

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:2

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Epithelial recurrent erosion dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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