rs116003670
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_000093.5(COL5A1):c.194G>A(p.Arg65Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,613,810 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R65W) has been classified as Likely benign.
Frequency
Consequence
NM_000093.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.194G>A | p.Arg65Gln | missense_variant | 2/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.194G>A | p.Arg65Gln | missense_variant | 2/66 | ||
COL5A1 | XM_017014266.3 | c.194G>A | p.Arg65Gln | missense_variant | 2/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.194G>A | p.Arg65Gln | missense_variant | 2/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.194G>A | p.Arg65Gln | missense_variant | 2/66 | 2 | A2 | ||
COL5A1 | ENST00000464187.1 | n.380G>A | non_coding_transcript_exon_variant | 2/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00152 AC: 232AN: 152248Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.000390 AC: 98AN: 251152Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135852
GnomAD4 exome AF: 0.000159 AC: 233AN: 1461444Hom.: 0 Cov.: 32 AF XY: 0.000139 AC XY: 101AN XY: 727000
GnomAD4 genome ? AF: 0.00153 AC: 233AN: 152366Hom.: 2 Cov.: 33 AF XY: 0.00119 AC XY: 89AN XY: 74504
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 22, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 08, 2024 | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
COL5A1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 25, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Fibromuscular dysplasia, multifocal Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 22, 2015 | This alteration is classified as 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2021 | This variant is associated with the following publications: (PMID: 28346524) - |
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at