chr3-48587833-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. P939P) has been classified as Likely 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:9

Conservation

PhyloP100: -7.34

Publications

29 publications found

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 Gene-Disease associations (from GenCC):

epidermolysis bullosa with congenital localized absence of skin and deformity of nails
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
dystrophic epidermolysis bullosa pruriginosa
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet
recessive dystrophic epidermolysis bullosa
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Genomics England PanelApp, Ambry Genetics, G2P, ClinGen
generalized dominant dystrophic epidermolysis bullosa
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet
pretibial dystrophic epidermolysis bullosa
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
transient bullous dermolysis of the newborn
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
acral dystrophic epidermolysis bullosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dystrophic epidermolysis bullosa, nails only
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
recessive dystrophic epidermolysis bullosa inversa
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
recessive dystrophic epidermolysis bullosa-generalized other
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COL7A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 255107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
COL7A1	NM_000094.4 link	c.2817A>G	p.Pro939Pro	synonymous_variant	Exon 22 of 119	ENST00000681320.1	NP_000085.1	Q02388-1Q59F16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL7A1	ENST00000681320.1 link	c.2817A>G	p.Pro939Pro	synonymous_variant	Exon 22 of 119		NM_000094.4	ENSP00000506558.1		Q02388-1
COL7A1	ENST00000328333.12 link	c.2817A>G	p.Pro939Pro	synonymous_variant	Exon 21 of 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

GnomAD2 exomes

AF:

0.674

AC:

168499

AN:

250106

AF XY:

0.673

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 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

African (AFR)

AF:

0.912

AC:

30539

AN:

33480

American (AMR)

AF:

0.587

AC:

26202

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.820

AC:

21421

AN:

26134

East Asian (EAS)

AF:

0.391

AC:

15509

AN:

39692

South Asian (SAS)

AF:

0.659

AC:

56841

AN:

86252

European-Finnish (FIN)

AF:

0.722

AC:

38117

AN:

52822

Middle Eastern (MID)

AF:

0.699

AC:

4030

AN:

5762

European-Non Finnish (NFE)

AF:

0.707

AC:

786151

AN:

1111912

Other (OTH)

AF:

0.708

AC:

42776

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

18750

37500

56251

75001

93751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19782

39564

59346

79128

98910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.739

AC:

112337

AN:

151924

Hom.:

42665

Cov.:

AF XY:

0.734

AC XY:

54529

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.902

AC:

37400

AN:

41444

American (AMR)

AF:

0.608

AC:

9301

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.826

AC:

2868

AN:

3472

East Asian (EAS)

AF:

0.377

AC:

1937

AN:

5136

South Asian (SAS)

AF:

0.659

AC:

3173

AN:

4812

European-Finnish (FIN)

AF:

0.736

AC:

7785

AN:

10574

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.700

AC:

47535

AN:

67888

Other (OTH)

AF:

0.716

AC:

1508

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1375

2749

4124

5498

6873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.716

Hom.:

64330

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:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jan 27, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epidermolysis bullosa dystrophica

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Nov 18, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.077

(source)

DANN

Benign

0.28

PhyloP100

-7.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over