3-48587833-T-C

Position:

chr3-48587833-T-C

Variant summary

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

The NM_000094.4(COL7A1):c.2817A>G(p.Pro939Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 1,613,022 control chromosomes in the GnomAD database, including 403,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42665 hom., cov: 30)

Exomes 𝑓: 0.70 ( 361254 hom. )

Consequence

COL7A1
NM_000094.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -7.34

Variant links:

Genes affected

COL7A1 (HGNC:2214): (collagen type VII alpha 1 chain) This gene encodes the alpha chain of type VII collagen. The type VII collagen fibril, composed of three identical alpha collagen chains, is restricted to the basement zone beneath stratified squamous epithelia. It functions as an anchoring fibril between the external epithelia and the underlying stroma. Mutations in this gene are associated with all forms of dystrophic epidermolysis bullosa. In the absence of mutations, however, an acquired form of this disease can result from an autoimmune response made to type VII collagen. [provided by RefSeq, Jul 2008]

COL7A1 links:

COL7A1 (HGNC:):

COL7A1 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=-0.99).

BP6

Variant 3-48587833-T-C is Benign according to our data. Variant chr3-48587833-T-C is described in ClinVar as [Benign]. Clinvar id is 255107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-48587833-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-7.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL7A1	NM_000094.4 linkuse as main transcript	c.2817A>G	p.Pro939Pro	synonymous_variant	22/119	ENST00000681320.1	NP_000085.1	Q02388-1Q59F16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL7A1	ENST00000681320.1 linkuse as main transcript	c.2817A>G	p.Pro939Pro	synonymous_variant	22/119		NM_000094.4	ENSP00000506558.1		Q02388-1
COL7A1	ENST00000328333.12 linkuse as main transcript	c.2817A>G	p.Pro939Pro	synonymous_variant	21/118	1		ENSP00000332371.8		Q02388-1

Frequencies

GnomAD3 genomes

AF:

0.739

AC:

112246

AN:

151806

Hom.:

42620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.902

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.826

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.736

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.714

GnomAD3 exomes

AF:

0.674

AC:

168499

AN:

250106

Hom.:

58402

AF XY:

0.673

AC XY:

91164

AN XY:

135428

show subpopulations

Gnomad AFR exome

AF:

0.907

Gnomad AMR exome

AF:

0.589

Gnomad ASJ exome

AF:

0.820

Gnomad EAS exome

AF:

0.376

Gnomad SAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.731

Gnomad NFE exome

AF:

0.695

Gnomad OTH exome

AF:

0.696

GnomAD4 exome

AF:

0.699

AC:

1021586

AN:

1461098

Hom.:

361254

Cov.:

AF XY:

0.698

AC XY:

507156

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.912

Gnomad4 AMR exome

AF:

0.587

Gnomad4 ASJ exome

AF:

0.820

Gnomad4 EAS exome

AF:

0.391

Gnomad4 SAS exome

AF:

0.659

Gnomad4 FIN exome

AF:

0.722

Gnomad4 NFE exome

AF:

0.707

Gnomad4 OTH exome

AF:

0.708

GnomAD4 genome

AF:

0.739

AC:

112337

AN:

151924

Hom.:

42665

Cov.:

AF XY:

0.734

AC XY:

54529

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.902

Gnomad4 AMR

AF:

0.608

Gnomad4 ASJ

AF:

0.826

Gnomad4 EAS

AF:

0.377

Gnomad4 SAS

AF:

0.659

Gnomad4 FIN

AF:

0.736

Gnomad4 NFE

AF:

0.700

Gnomad4 OTH

AF:

0.716

Alfa

AF:

0.725

Hom.:

18888

Bravo

AF:

0.737

Asia WGS

AF:

0.596

AC:

2074

AN:

3476

EpiCase

AF:

0.700

EpiControl

AF:

0.699

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

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

Epidermolysis bullosa dystrophica

Benign:2

Benign, 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 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, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 18, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.077

DANN

Benign

0.28

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