chr3-48587178-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000094.4(COL7A1):c.3139+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,612,868 control chromosomes in the GnomAD database, including 107,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 18533 hom., cov: 31)

Exomes 𝑓: 0.34 ( 89321 hom. )

Consequence

COL7A1
NM_000094.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.57

Publications

15 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 3-48587178-C-T is Benign according to our data. Variant chr3-48587178-C-T is described in CliVar as Benign. Clinvar id is 255108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-48587178-C-T is described in CliVar as Benign. Clinvar id is 255108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-48587178-C-T is described in CliVar as Benign. Clinvar id is 255108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL7A1	NM_000094.4 link	c.3139+12G>A		intron_variant	Intron 24 of 118	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.3139+12G>A		intron_variant	Intron 24 of 118		NM_000094.4	ENSP00000506558.1		Q02388-1
COL7A1	ENST00000328333.12 link	c.3139+12G>A		intron_variant	Intron 23 of 117	1		ENSP00000332371.8		Q02388-1

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68175

AN:

151740

Hom.:

18494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.395

GnomAD2 exomes

AF:

0.340

AC:

84800

AN:

249290

AF XY:

0.338

show subpopulations

Gnomad AFR exome

AF:

0.773

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.338

AC:

494159

AN:

1461010

Hom.:

89321

Cov.:

AF XY:

0.337

AC XY:

245156

AN XY:

726742

show subpopulations

African (AFR)

AF:

0.786

AC:

26302

AN:

33464

American (AMR)

AF:

0.205

AC:

9141

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

9748

AN:

26114

East Asian (EAS)

AF:

0.126

AC:

5008

AN:

39694

South Asian (SAS)

AF:

0.366

AC:

31552

AN:

86152

European-Finnish (FIN)

AF:

0.442

AC:

23508

AN:

53162

Middle Eastern (MID)

AF:

0.310

AC:

1786

AN:

5766

European-Non Finnish (NFE)

AF:

0.329

AC:

365386

AN:

1111664

Other (OTH)

AF:

0.360

AC:

21728

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

22806

45612

68419

91225

114031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11900

23800

35700

47600

59500

<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:

0.449

AC:

68259

AN:

151858

Hom.:

18533

Cov.:

AF XY:

0.447

AC XY:

33178

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.766

AC:

31738

AN:

41418

American (AMR)

AF:

0.265

AC:

4051

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1324

AN:

3464

East Asian (EAS)

AF:

0.160

AC:

824

AN:

5146

South Asian (SAS)

AF:

0.360

AC:

1727

AN:

4802

European-Finnish (FIN)

AF:

0.455

AC:

4799

AN:

10556

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.332

AC:

22534

AN:

67882

Other (OTH)

AF:

0.394

AC:

833

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1598

3195

4793

6390

7988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.349

Hom.:

17442

Bravo

AF:

0.446

Asia WGS

AF:

0.318

AC:

1111

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

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

- -

Epidermolysis bullosa dystrophica

Benign:1

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.20

(source)

DANN

Benign

0.50

PhyloP100

-1.6

Mutation Taster

=99/1

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

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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