rs74390291

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000094.4(COL7A1):c.4483-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,613,966 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 106 hom. )

Consequence

COL7A1
NM_000094.4 intron

Scores

Splicing: ADA: 0.5456

Clinical Significance

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

Conservation

PhyloP100: 1.03

Publications

3 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=-0.65).

BP6

Variant 3-48583059-A-G is Benign according to our data. Variant chr3-48583059-A-G is described in ClinVar as Benign. ClinVar VariationId is 255110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00771 (1173/152138) while in subpopulation NFE AF = 0.0116 (791/67972). AF 95% confidence interval is 0.011. There are 9 homozygotes in GnomAd4. There are 598 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL7A1	NM_000094.4 link	c.4483-11T>C		intron_variant	Intron 43 of 118	ENST00000681320.1	NP_000085.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COL7A1	ENST00000681320.1 link	c.4483-11T>C	intron_variant	Intron 43 of 118		NM_000094.4	ENSP00000506558.1
COL7A1	ENST00000328333.12 link	c.4483-11T>C	intron_variant	Intron 42 of 117	1		ENSP00000332371.8
COL7A1	ENST00000487017.5 link	n.400-11T>C	intron_variant	Intron 8 of 82	5

Frequencies

GnomAD3 genomes

AF:

0.00772

AC:

1173

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00225

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.0152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00622

GnomAD2 exomes

AF:

0.00768

AC:

1930

AN:

251416

AF XY:

0.00770

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00414

Gnomad ASJ exome

AF:

0.00844

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0136

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00994

GnomAD4 exome

AF:

0.0113

AC:

16503

AN:

1461828

Hom.:

106

Cov.:

AF XY:

0.0110

AC XY:

8001

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.00170

AC:

AN:

33480

American (AMR)

AF:

0.00436

AC:

195

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00869

AC:

227

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00374

AC:

323

AN:

86258

European-Finnish (FIN)

AF:

0.0129

AC:

688

AN:

53380

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0129

AC:

14328

AN:

1112000

Other (OTH)

AF:

0.0112

AC:

678

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1082

2164

3245

4327

5409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.00771

AC:

1173

AN:

152138

Hom.:

Cov.:

AF XY:

0.00804

AC XY:

598

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

41500

American (AMR)

AF:

0.00477

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00270

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0152

AC:

161

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0116

AC:

791

AN:

67972

Other (OTH)

AF:

0.00616

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00818

Hom.:

Bravo

AF:

0.00666

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

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

Sep 29, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

-0.65

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.55

dbscSNV1_RF

Benign

0.42

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