rs537768945
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BS1BS2
The NM_000093.5(COL5A1):c.4473C>T(p.Ile1491=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 1,613,978 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00016 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00039 ( 11 hom. )
Consequence
COL5A1
NM_000093.5 synonymous
NM_000093.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.842
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 -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.18).
BP6
?
Variant 9-134820142-C-T is Benign according to our data. Variant chr9-134820142-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 516607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.842 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000395 (577/1461616) while in subpopulation SAS AF= 0.0041 (354/86248). AF 95% confidence interval is 0.00375. There are 11 homozygotes in gnomad4_exome. There are 377 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.4473C>T | p.Ile1491= | synonymous_variant | 58/66 | ENST00000371817.8 | |
LOC101448202 | NR_103451.2 | n.138G>A | non_coding_transcript_exon_variant | 2/2 | |||
COL5A1 | NM_001278074.1 | c.4473C>T | p.Ile1491= | synonymous_variant | 58/66 | ||
COL5A1 | XM_017014266.3 | c.4473C>T | p.Ile1491= | synonymous_variant | 58/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.4473C>T | p.Ile1491= | synonymous_variant | 58/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.4473C>T | p.Ile1491= | synonymous_variant | 58/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152244Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000633 AC: 159AN: 251380Hom.: 6 AF XY: 0.000802 AC XY: 109AN XY: 135900
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GnomAD4 exome AF: 0.000395 AC: 577AN: 1461616Hom.: 11 Cov.: 30 AF XY: 0.000518 AC XY: 377AN XY: 727128
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152362Hom.: 1 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, classic type, 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 12, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 24, 2023 | - - |
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
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 10, 2020 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 15, 2021 | - - |
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