chr3-48566719-C-A
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000094.4(COL7A1):c.8245G>T(p.Gly2749Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000657 in 152,190 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 Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
COL7A1
NM_000094.4 stop_gained
NM_000094.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.53
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-48566719-C-A is Pathogenic according to our data. Variant chr3-48566719-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2579680.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL7A1 | NM_000094.4 | c.8245G>T | p.Gly2749Ter | stop_gained | 112/119 | ENST00000681320.1 | NP_000085.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL7A1 | ENST00000681320.1 | c.8245G>T | p.Gly2749Ter | stop_gained | 112/119 | NM_000094.4 | ENSP00000506558 | P1 | ||
COL7A1 | ENST00000328333.12 | c.8245G>T | p.Gly2749Ter | stop_gained | 111/118 | 1 | ENSP00000332371 | P1 | ||
COL7A1 | ENST00000474432.1 | n.645G>T | non_coding_transcript_exon_variant | 1/2 | 3 | |||||
COL7A1 | ENST00000487017.5 | n.4884G>T | non_coding_transcript_exon_variant | 76/83 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152072Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 37
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74396
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Recessive dystrophic epidermolysis bullosa Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Narges Medical Genetic and Prenatal Diagnosis Lab | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at