rs3827848
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_000093.5(COL5A1):c.4122G>A(p.Thr1374=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,610 control chromosomes in the GnomAD database, including 19,278 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000093.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.4122G>A | p.Thr1374= | splice_region_variant, synonymous_variant | 52/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.4122G>A | p.Thr1374= | splice_region_variant, synonymous_variant | 52/66 | ||
COL5A1 | XM_017014266.3 | c.4122G>A | p.Thr1374= | splice_region_variant, synonymous_variant | 52/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.4122G>A | p.Thr1374= | splice_region_variant, synonymous_variant | 52/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.4122G>A | p.Thr1374= | splice_region_variant, synonymous_variant | 52/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.140 AC: 21362AN: 152044Hom.: 1606 Cov.: 33
GnomAD3 exomes AF: 0.147 AC: 36952AN: 251360Hom.: 2888 AF XY: 0.147 AC XY: 19954AN XY: 135876
GnomAD4 exome AF: 0.153 AC: 223574AN: 1461448Hom.: 17670 Cov.: 34 AF XY: 0.153 AC XY: 111168AN XY: 727038
GnomAD4 genome ? AF: 0.141 AC: 21386AN: 152162Hom.: 1608 Cov.: 33 AF XY: 0.139 AC XY: 10307AN XY: 74390
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 13, 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 10, 2017 | Variant summary: The COL5A1 c.4122G>A (p.Thr1374Thr) variant causes a missense change involving 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 weakening the canonical donor cite. However, these predictions have yet to be confirmed by functional studies. This variant was found in 17922/121286 control chromosomes (1465 homozygotes) at a frequency of 0.1477664, which is approximately 118213 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. - |
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 | Feb 04, 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
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at