rs75648697
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_000093.5(COL5A1):c.850G>A(p.Glu284Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000867 in 1,614,182 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E284G) has been classified as Benign.
Frequency
Consequence
NM_000093.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.850G>A | p.Glu284Lys | missense_variant | 6/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.850G>A | p.Glu284Lys | missense_variant | 6/66 | ||
COL5A1 | XM_017014266.3 | c.850G>A | p.Glu284Lys | missense_variant | 6/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.850G>A | p.Glu284Lys | missense_variant | 6/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.850G>A | p.Glu284Lys | missense_variant | 6/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000454 AC: 114AN: 251374Hom.: 1 AF XY: 0.000375 AC XY: 51AN XY: 135878
GnomAD4 exome AF: 0.0000800 AC: 117AN: 1461866Hom.: 2 Cov.: 34 AF XY: 0.0000743 AC XY: 54AN XY: 727236
GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74464
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome type 7A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 08, 2017 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Ehlers-Danlos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 01, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2020 | - - |
Ehlers-Danlos syndrome, classic type Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at