2-188995732-C-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS1
The NM_000090.4(COL3A1):c.1550C>T(p.Pro517Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000174 in 1,565,876 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000090.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.1550C>T | p.Pro517Leu | missense_variant | Exon 22 of 51 | ENST00000304636.9 | NP_000081.2 | |
MIR3606 | NR_037401.1 | n.*40C>T | downstream_gene_variant | |||||
MIR3606 | unassigned_transcript_524 | n.*41C>T | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.1550C>T | p.Pro517Leu | missense_variant | Exon 22 of 51 | 1 | NM_000090.4 | ENSP00000304408.4 | ||
COL3A1 | ENST00000450867.2 | c.1451C>T | p.Pro484Leu | missense_variant | Exon 21 of 50 | 1 | ENSP00000415346.2 | |||
MIR3606 | ENST00000637672.1 | n.*40C>T | downstream_gene_variant | 6 |
Frequencies
GnomAD3 genomes AF: 0.000783 AC: 119AN: 151906Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000199 AC: 35AN: 175832Hom.: 0 AF XY: 0.000193 AC XY: 18AN XY: 93374
GnomAD4 exome AF: 0.000108 AC: 153AN: 1413852Hom.: 1 Cov.: 30 AF XY: 0.0000973 AC XY: 68AN XY: 698612
GnomAD4 genome AF: 0.000783 AC: 119AN: 152024Hom.: 0 Cov.: 31 AF XY: 0.000767 AC XY: 57AN XY: 74308
ClinVar
Submissions by phenotype
not specified Benign:4
The p.Pro517Leu variant in COL3A1 is classified as likely benign because it has been identified in 0.3% (51/19014) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1. -
- -
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 Uncertain:1Benign:2
- -
- -
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, type 4 Uncertain:1Benign:2
- -
- -
- -
not provided Benign:2
COL3A1: BS1 -
Variant summary: The COL3A1 c.1550C>T (p.Pro517Leu) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 18/22204 control chromosomes at a frequency of 0.0008107, which is approximately 649 times the estimated maximal expected allele frequency of a pathogenic COL3A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. This variant has been identified in one patient with vascular Ehlers-Danlos syndrome, who also carries COL3A1 p.G912A (classified as causal in the paper, Drera_2011). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at