rs147729713
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_000093.5(COL5A1):c.804C>T(p.Gly268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,613,994 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00020 ( 1 hom. )
Consequence
COL5A1
NM_000093.5 synonymous
NM_000093.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.60
Genes affected
COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 9-134728687-C-T is Benign according to our data. Variant chr9-134728687-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212921.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=4, Benign=1}.
BP7
?
Synonymous conserved (PhyloP=-3.6 with no splicing effect.
BS2
?
High AC in GnomAd4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.804C>T | p.Gly268= | synonymous_variant | 6/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.804C>T | p.Gly268= | synonymous_variant | 6/66 | ||
COL5A1 | XM_017014266.3 | c.804C>T | p.Gly268= | synonymous_variant | 6/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.804C>T | p.Gly268= | synonymous_variant | 6/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.804C>T | p.Gly268= | synonymous_variant | 6/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000994 AC: 25AN: 251388Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135878
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GnomAD4 exome AF: 0.000198 AC: 290AN: 1461802Hom.: 1 Cov.: 34 AF XY: 0.000195 AC XY: 142AN XY: 727214
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74342
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 10, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 03, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 16, 2022 | BS1, BP4, BP7, PS3_supporting - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | COL5A1: BP4, BP7 - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 09, 2023 | The c.804C>T variant (also known as p.G268G), located in coding exon 6, results from a C to T substitution at nucleotide position 804 of the COL5A1 gene. This nucleotide substitution does not change the amino acid at codon 268. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice donor site. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Based on data from gnomAD, the T allele has an overall frequency of 0.01% (28/282766) total alleles studied. The highest observed frequency was 0.02% (21/129140) of European (non-Finnish) alleles. This nucleotide position is not conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
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
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 05, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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