3-48590258-G-A
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000094.4(COL7A1):c.2005C>T(p.Arg669Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,740 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000094.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL7A1 | NM_000094.4 | c.2005C>T | p.Arg669Ter | stop_gained | 16/119 | ENST00000681320.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL7A1 | ENST00000681320.1 | c.2005C>T | p.Arg669Ter | stop_gained | 16/119 | NM_000094.4 | P1 | ||
COL7A1 | ENST00000328333.12 | c.2005C>T | p.Arg669Ter | stop_gained | 15/118 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249672Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135088
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461624Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727118
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
not provided Pathogenic:4
Pathogenic, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 08, 2021 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 19665875, 25525159, 19681861, 26076072, 9892921, 17073998, 9881948, 26148662, 26833212, 31001817, 29625052, 33274474, 32978145) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | This sequence change creates a premature translational stop signal (p.Arg669*) in the COL7A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL7A1 are known to be pathogenic (PMID: 16971478). This variant is present in population databases (rs780261665, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with autosomal recessive dystrophic epidermolysis bullosa (PMID: 9881948, 26076072, 26148662). ClinVar contains an entry for this variant (Variation ID: 374052). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Recessive dystrophic epidermolysis bullosa;C0268371:Dominant dystrophic epidermolysis bullosa with absence of skin;C0432321:Pretibial dystrophic epidermolysis bullosa;C0432322:Generalized dominant dystrophic epidermolysis bullosa;C1275114:Epidermolysis bullosa pruriginosa;C1843761:Nonsyndromic congenital nail disorder 8;C1851573:Transient bullous dermolysis of the newborn Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 20, 2022 | - - |
Abnormality of the skin;C0221260:Nail dystrophy;C3887524:Skin erosion Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2017 | - - |
Epidermolysis bullosa pruriginosa Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2016 | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2,PM3,PP3,PP4. - |
Recessive dystrophic epidermolysis bullosa Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Abnormal blistering of the skin Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2017 | - - |
Anonychia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2017 | - - |
Finger syndactyly;C0265660:Toe syndactyly;C0349588:Short stature;C4024876:Palmoplantar blistering Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Oct 21, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at