3-48575475-C-T

Position:

chr3-48575475-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PP2PP3_StrongPP5_Moderate

The NM_000094.4(COL7A1):c.6044G>A(p.Gly2015Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COL7A1
NM_000094.4 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 6.11

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), COL7A1. . Gene score misZ 1.5899 (greater than the threshold 3.09). Trascript score misZ 4.0428 (greater than threshold 3.09). GenCC has associacion of gene with recessive dystrophic epidermolysis bullosa, dystrophic epidermolysis bullosa pruriginosa, recessive dystrophic epidermolysis bullosa-generalized other, transient bullous dermolysis of the newborn, epidermolysis bullosa with congenital localized absence of skin and deformity of nails, generalized dominant dystrophic epidermolysis bullosa, dystrophic epidermolysis bullosa, nails only, acral dystrophic epidermolysis bullosa, recessive dystrophic epidermolysis bullosa inversa, pretibial dystrophic epidermolysis bullosa.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.991

PP5

Variant 3-48575475-C-T is Pathogenic according to our data. Variant chr3-48575475-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 17449.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL7A1	NM_000094.4 linkuse as main transcript	c.6044G>A	p.Gly2015Glu	missense_variant	74/119	ENST00000681320.1	NP_000085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL7A1	ENST00000681320.1 linkuse as main transcript	c.6044G>A	p.Gly2015Glu	missense_variant	74/119		NM_000094.4	ENSP00000506558	P1	Q02388-1
COL7A1	ENST00000328333.12 linkuse as main transcript	c.6044G>A	p.Gly2015Glu	missense_variant	73/118	1		ENSP00000332371	P1	Q02388-1
COL7A1	ENST00000487017.5 linkuse as main transcript	n.1961G>A		non_coding_transcript_exon_variant	39/83	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241260

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132084

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000933

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459698

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Recessive dystrophic epidermolysis bullosa

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota

Dec 01, 2016

- -

Generalized dominant dystrophic epidermolysis bullosa

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 24, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Pathogenic

0.85

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.76

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

0.96

MutationAssessor

Pathogenic

4.2

MutationTaster

Benign

1.0

A;A

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.2

REVEL

Pathogenic

0.96

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.98

MutPred

0.93

Loss of glycosylation at P2017 (P = 0.032);

MVP

0.99

MPC

0.32

ClinPred

1.0

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.70

gMVP

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over