rs754015151
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000090.4(COL3A1):c.2724G>A(p.Ala908=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,460,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
COL3A1
NM_000090.4 synonymous
NM_000090.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.554
Genes affected
COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 2-189004044-G-A is Benign according to our data. Variant chr2-189004044-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 459776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.554 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.2724G>A | p.Ala908= | synonymous_variant | 39/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.2724G>A | p.Ala908= | synonymous_variant | 39/51 | 1 | NM_000090.4 | P1 | |
COL3A1 | ENST00000450867.2 | c.2625G>A | p.Ala875= | synonymous_variant | 38/50 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250094Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135438
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460858Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 726718
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, type 4 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 15, 2023 | This synonymous variant does not change the amino acid sequence of the COL3A1 protein. However, computational splicing tools suggest that this variant may disrupt RNA splicing. To our knowledge, functional studies have not been performed to investigate this prediction. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/250094 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2022 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 25, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at