rs779774302
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS1
The NM_000090.4(COL3A1):c.4086C>T(p.Ser1362=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,002 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
COL3A1
NM_000090.4 synonymous
NM_000090.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.274
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
?
Variant 2-189010722-C-T is Benign according to our data. Variant chr2-189010722-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 197910.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=6, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.274 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000158 (24/152166) while in subpopulation AFR AF= 0.000434 (18/41430). AF 95% confidence interval is 0.00028. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.4086C>T | p.Ser1362= | synonymous_variant | 50/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.4086C>T | p.Ser1362= | synonymous_variant | 50/51 | 1 | NM_000090.4 | P1 | |
COL3A1 | ENST00000450867.2 | c.3987C>T | p.Ser1329= | synonymous_variant | 49/50 | 1 | |||
COL3A1 | ENST00000487010.1 | n.1465C>T | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152166Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251204Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135746
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461836Hom.: 0 Cov.: 35 AF XY: 0.0000206 AC XY: 15AN XY: 727218
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152166Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74334
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 28, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2018 | 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. - |
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2015 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 16, 2018 | - - |
Ehlers-Danlos syndrome, type 4 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 24, 2017 | - - |
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