9-134798472-A-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000371817.8(COL5A1):c.2952+11A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,612,640 control chromosomes in the GnomAD database, including 207,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.52 ( 20544 hom., cov: 33)
Exomes 𝑓: 0.50 ( 187268 hom. )
Consequence
COL5A1
ENST00000371817.8 intron
ENST00000371817.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.10
Genes affected
COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 9-134798472-A-T is Benign according to our data. Variant chr9-134798472-A-T is described in ClinVar as [Benign]. Clinvar id is 136877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134798472-A-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.2952+11A>T | intron_variant | ENST00000371817.8 | NP_000084.3 | |||
COL5A1 | NM_001278074.1 | c.2952+11A>T | intron_variant | NP_001265003.1 | ||||
COL5A1 | XM_017014266.3 | c.2952+11A>T | intron_variant | XP_016869755.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.2952+11A>T | intron_variant | 1 | NM_000093.5 | ENSP00000360882.3 | ||||
COL5A1 | ENST00000371820.4 | c.2952+11A>T | intron_variant | 2 | ENSP00000360885.4 |
Frequencies
GnomAD3 genomes AF: 0.516 AC: 78460AN: 151978Hom.: 20542 Cov.: 33
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GnomAD3 exomes AF: 0.520 AC: 130255AN: 250676Hom.: 34968 AF XY: 0.518 AC XY: 70276AN XY: 135656
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GnomAD4 exome AF: 0.503 AC: 734686AN: 1460544Hom.: 187268 Cov.: 38 AF XY: 0.504 AC XY: 366347AN XY: 726668
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GnomAD4 genome AF: 0.516 AC: 78506AN: 152096Hom.: 20544 Cov.: 33 AF XY: 0.514 AC XY: 38208AN XY: 74332
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 02, 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, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
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.2952+11A>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 3/5 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 63233/120718 control chromosomes at a frequency of 0.5238076, which is approximately 419046 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. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign. - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Fibromuscular dysplasia, multifocal Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Ehlers-Danlos syndrome type 7A Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at