NM_000094.4:c.8305-20G>C

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.8305-20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 1,614,112 control chromosomes in the GnomAD database, including 3,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 268 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3429 hom. )

Consequence

COL7A1
NM_000094.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.664

Publications

9 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=-0.79).

BP6

Variant 3-48566583-C-G is Benign according to our data. Variant chr3-48566583-C-G is described in ClinVar as [Benign]. Clinvar id is 255114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL7A1	NM_000094.4 link	c.8305-20G>C		intron_variant	Intron 112 of 118	ENST00000681320.1	NP_000085.1	Q02388-1Q59F16

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL7A1	ENST00000681320.1 link	c.8305-20G>C	intron_variant	Intron 112 of 118		NM_000094.4	ENSP00000506558.1	Q02388-1
COL7A1	ENST00000328333.12 link	c.8305-20G>C	intron_variant	Intron 111 of 117	1		ENSP00000332371.8	Q02388-1
COL7A1	ENST00000474432.1 link	n.705-20G>C	intron_variant	Intron 1 of 1	3
COL7A1	ENST00000487017.5 link	n.4944-20G>C	intron_variant	Intron 76 of 82	5

Frequencies

GnomAD3 genomes

AF:

0.0509

AC:

7738

AN:

152150

Hom.:

268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0453

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.0877

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0736

Gnomad OTH

AF:

0.0459

GnomAD2 exomes

AF:

0.0539

AC:

13542

AN:

251462

AF XY:

0.0540

show subpopulations

Gnomad AFR exome

AF:

0.0126

Gnomad AMR exome

AF:

0.0318

Gnomad ASJ exome

AF:

0.0722

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0898

Gnomad NFE exome

AF:

0.0763

Gnomad OTH exome

AF:

0.0586

GnomAD4 exome

AF:

0.0662

AC:

96820

AN:

1461844

Hom.:

3429

Cov.:

AF XY:

0.0650

AC XY:

47252

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0102

AC:

340

AN:

33480

American (AMR)

AF:

0.0334

AC:

1493

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

1860

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0192

AC:

1659

AN:

86258

European-Finnish (FIN)

AF:

0.0882

AC:

4712

AN:

53418

Middle Eastern (MID)

AF:

0.0376

AC:

217

AN:

5766

European-Non Finnish (NFE)

AF:

0.0747

AC:

83041

AN:

1111972

Other (OTH)

AF:

0.0579

AC:

3494

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

5853

11705

17558

23410

29263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2938

5876

8814

11752

14690

<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:

0.0508

AC:

7734

AN:

152268

Hom.:

268

Cov.:

AF XY:

0.0508

AC XY:

3784

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0138

AC:

573

AN:

41558

American (AMR)

AF:

0.0453

AC:

694

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

245

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0218

AC:

105

AN:

4822

European-Finnish (FIN)

AF:

0.0877

AC:

931

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0736

AC:

5005

AN:

67994

Other (OTH)

AF:

0.0449

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

385

771

1156

1542

1927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0629

Hom.:

Bravo

AF:

0.0469

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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