rs149722210
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS1
The NM_000090.4(COL3A1):c.3133G>A(p.Ala1045Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,614,126 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000090.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 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.3133G>A | p.Ala1045Thr | missense_variant | Exon 43 of 51 | 1 | NM_000090.4 | ENSP00000304408.4 | ||
COL3A1 | ENST00000450867.2 | c.3034G>A | p.Ala1012Thr | missense_variant | Exon 42 of 50 | 1 | ENSP00000415346.2 |
Frequencies
GnomAD3 genomes AF: 0.000368 AC: 56AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000573 AC: 144AN: 251364Hom.: 0 AF XY: 0.000574 AC XY: 78AN XY: 135866
GnomAD4 exome AF: 0.000276 AC: 403AN: 1461882Hom.: 1 Cov.: 33 AF XY: 0.000307 AC XY: 223AN XY: 727244
GnomAD4 genome AF: 0.000368 AC: 56AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74446
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:3
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Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.5% (46/8636) East Asian; ClinVar: 1 VUS, 1 LB; Path for nonsense at same codon -
not provided Benign:4
Variant summary: The COL3A1 c.3133G>A (p.Ala1045Thr) variant involves the alteration of a non-conserved nucleotide and 3/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a damaging outcome. However, these predictions have yet to be functionally assessed. This variant was found in 71/121484 control chromosomes at a frequency of 0.0005844, which is approximately 468 times the estimated maximal expected allele frequency of a pathogenic COL3A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories classified this variant as likely benign/benign. Taken together, this variant is classified as benign. -
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This variant is associated with the following publications: (PMID: 22001912, 25834947, 30115950, 27888582, 32123317) -
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Ehlers-Danlos syndrome, type 4 Benign:4
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
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Familial thoracic aortic aneurysm and aortic dissection Benign:3
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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. -
Ehlers-Danlos syndrome Benign:1
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Connective tissue disorder Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at