3-48573192-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000094.4(COL7A1):c.6696C>A(p.Pro2232Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,614,014 control chromosomes in the GnomAD database, including 295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P2232P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.012 ( 14 hom., cov: 32)

Exomes 𝑓: 0.018 ( 281 hom. )

Consequence

COL7A1
NM_000094.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:7

Conservation

PhyloP100: -0.228

Publications

4 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=-0.69).

BP6

Variant 3-48573192-G-T is Benign according to our data. Variant chr3-48573192-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.228 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0119 (1805/152310) while in subpopulation NFE AF = 0.0195 (1327/68010). AF 95% confidence interval is 0.0186. There are 14 homozygotes in GnomAd4. There are 868 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000094.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL7A1	NM_000094.4	MANE Select	c.6696C>A	p.Pro2232Pro	synonymous	Exon 85 of 119	NP_000085.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL7A1	ENST00000681320.1	MANE Select	c.6696C>A	p.Pro2232Pro	synonymous	Exon 85 of 119	ENSP00000506558.1
COL7A1	ENST00000328333.12	TSL:1	c.6696C>A	p.Pro2232Pro	synonymous	Exon 84 of 118	ENSP00000332371.8
COL7A1	ENST00000487017.5	TSL:5	n.2613C>A		non_coding_transcript_exon	Exon 50 of 83

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1805

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00889

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0195

Gnomad OTH

AF:

0.00861

GnomAD2 exomes

AF:

0.0125

AC:

3128

AN:

250482

AF XY:

0.0130

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.00556

Gnomad ASJ exome

AF:

0.00838

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00897

Gnomad NFE exome

AF:

0.0196

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.0184

AC:

26913

AN:

1461704

Hom.:

281

Cov.:

AF XY:

0.0182

AC XY:

13223

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.00257

AC:

AN:

33480

American (AMR)

AF:

0.00566

AC:

253

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00895

AC:

234

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.0114

AC:

981

AN:

86250

European-Finnish (FIN)

AF:

0.0100

AC:

535

AN:

53332

Middle Eastern (MID)

AF:

0.00485

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0215

AC:

23907

AN:

1111936

Other (OTH)

AF:

0.0147

AC:

886

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1827

3654

5482

7309

9136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.0119

AC:

1805

AN:

152310

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

868

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00320

AC:

133

AN:

41564

American (AMR)

AF:

0.00888

AC:

136

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0122

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00885

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0195

AC:

1327

AN:

68010

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

181

271

362

452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0133

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0176

EpiControl

AF:

0.0175

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Sep 11, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

PreventionGenetics, part of Exact Sciences

Significance:Likely 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

Epidermolysis bullosa dystrophica

Uncertain:1Benign: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.

Jan 17, 2020

Natera, Inc.

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely 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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.12

(source)

DANN

Benign

0.41

PhyloP100

-0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over