chr9-134730403-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000093.5(COL5A1):c.1092C>T(p.Pro364=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,614,132 control chromosomes in the GnomAD database, including 2,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P364P) has been classified as Likely benign.
Frequency
Consequence
NM_000093.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.1092C>T | p.Pro364= | synonymous_variant | 7/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.1092C>T | p.Pro364= | synonymous_variant | 7/66 | ||
COL5A1 | XM_017014266.3 | c.1092C>T | p.Pro364= | synonymous_variant | 7/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.1092C>T | p.Pro364= | synonymous_variant | 7/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.1092C>T | p.Pro364= | synonymous_variant | 7/66 | 2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0787 AC: 11974AN: 152164Hom.: 1207 Cov.: 34
GnomAD3 exomes AF: 0.0386 AC: 9704AN: 251280Hom.: 730 AF XY: 0.0380 AC XY: 5164AN XY: 135848
GnomAD4 exome AF: 0.0226 AC: 33033AN: 1461850Hom.: 1759 Cov.: 35 AF XY: 0.0241 AC XY: 17532AN XY: 727234
GnomAD4 genome AF: 0.0788 AC: 12005AN: 152282Hom.: 1217 Cov.: 34 AF XY: 0.0768 AC XY: 5720AN XY: 74466
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 16, 2012 | 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. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Fibromuscular dysplasia, multifocal Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 02, 2015 | 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. - |
Ehlers-Danlos syndrome type 7A Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 15, 2017 | Variant summary: The COL5A1 c.1092C>T (p.Pro364Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 5362/121014 control chromosomes (451 homozygotes) at a frequency of 0.0443089, which is approximately 35447 times the estimated maximal expected allele frequency of a pathogenic COL5A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at