rs2228559
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_000093.5(COL5A1):c.4560C>T(p.Ile1520=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0285 in 1,613,196 control chromosomes in the GnomAD database, including 793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.035 ( 118 hom., cov: 33)
Exomes 𝑓: 0.028 ( 675 hom. )
Consequence
COL5A1
NM_000093.5 synonymous
NM_000093.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.368
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant 9-134822102-C-T is Benign according to our data. Variant chr9-134822102-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134822102-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.368 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.4560C>T | p.Ile1520= | synonymous_variant | 59/66 | ENST00000371817.8 | |
LOC101448202 | NR_103451.2 | n.71-1893G>A | intron_variant, non_coding_transcript_variant | ||||
COL5A1 | NM_001278074.1 | c.4560C>T | p.Ile1520= | synonymous_variant | 59/66 | ||
COL5A1 | XM_017014266.3 | c.4560C>T | p.Ile1520= | synonymous_variant | 59/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.4560C>T | p.Ile1520= | synonymous_variant | 59/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.4560C>T | p.Ile1520= | synonymous_variant | 59/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0349 AC: 5305AN: 152166Hom.: 116 Cov.: 33
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GnomAD3 exomes AF: 0.0256 AC: 6429AN: 251446Hom.: 139 AF XY: 0.0250 AC XY: 3396AN XY: 135896
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GnomAD4 exome AF: 0.0278 AC: 40627AN: 1460912Hom.: 675 Cov.: 32 AF XY: 0.0275 AC XY: 19976AN XY: 726792
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GnomAD4 genome ? AF: 0.0349 AC: 5311AN: 152284Hom.: 118 Cov.: 33 AF XY: 0.0327 AC XY: 2436AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 29, 2012 | 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:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
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 | Jan 30, 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. - |
Ehlers-Danlos syndrome type 7A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Ehlers-Danlos syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 07, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 15, 2017 | Variant summary: The c.4560C>T (p.Ile1520=) in COL5A1 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect the normal splicing pattern, however no functional studies supporting these predictions were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.02718 (3299 /121364 chrs tested), including numerous homozygous occurrences. This frequency exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.000031). The variant of interest has been cited as Benign by multiple reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. - |
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