rs1801184
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000090.4(COL3A1):āc.2244T>Cā(p.Gly748Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,594,368 control chromosomes in the GnomAD database, including 61,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_000090.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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COL3A1 | ENST00000304636.9 | c.2244T>C | p.Gly748Gly | synonymous_variant | Exon 32 of 51 | 1 | NM_000090.4 | ENSP00000304408.4 | ||
COL3A1 | ENST00000450867.2 | c.2145T>C | p.Gly715Gly | synonymous_variant | Exon 31 of 50 | 1 | ENSP00000415346.2 |
Frequencies
GnomAD3 genomes AF: 0.272 AC: 41256AN: 151874Hom.: 5833 Cov.: 31
GnomAD3 exomes AF: 0.234 AC: 51452AN: 219808Hom.: 6705 AF XY: 0.235 AC XY: 27593AN XY: 117192
GnomAD4 exome AF: 0.272 AC: 392583AN: 1442374Hom.: 55824 Cov.: 35 AF XY: 0.270 AC XY: 192925AN XY: 715132
GnomAD4 genome AF: 0.272 AC: 41273AN: 151994Hom.: 5835 Cov.: 31 AF XY: 0.264 AC XY: 19649AN XY: 74304
ClinVar
Submissions by phenotype
not specified Benign:7
p.Gly748Gly in exon 32 of COL3A1: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 29% (2489/8596) of European American chromosomes and 28% (1217/4406) of African American chromos omes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; d bSNP rs1801184). -
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. -
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Variant summary: COL3A1 c.2244T>C alters a non-conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.23 in 219808 control chromosomes in the gnomAD database, including 6705 homozygotes, strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2244T>C in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
Ehlers-Danlos syndrome, type 4 Benign:4
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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Familial thoracic aortic aneurysm and aortic dissection Benign:2
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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. -
not provided Benign:2
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Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at