9-134818715-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000093.5(COL5A1):c.4290C>T(p.Ala1430Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000571 in 1,611,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000058 ( 0 hom. )
Consequence
COL5A1
NM_000093.5 synonymous
NM_000093.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.255
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 9-134818715-C-T is Benign according to our data. Variant chr9-134818715-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.255 with no splicing effect.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| COL5A1 | NM_000093.5 | c.4290C>T | p.Ala1430Ala | synonymous_variant | Exon 55 of 66 | ENST00000371817.8 | NP_000084.3 | |
| COL5A1 | NM_001278074.1 | c.4290C>T | p.Ala1430Ala | synonymous_variant | Exon 55 of 66 | NP_001265003.1 | ||
| COL5A1 | XM_017014266.3 | c.4290C>T | p.Ala1430Ala | synonymous_variant | Exon 55 of 65 | XP_016869755.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| COL5A1 | ENST00000371817.8 | c.4290C>T | p.Ala1430Ala | synonymous_variant | Exon 55 of 66 | 1 | NM_000093.5 | ENSP00000360882.3 | ||
| COL5A1 | ENST00000371820.4 | c.4290C>T | p.Ala1430Ala | synonymous_variant | Exon 55 of 66 | 2 | ENSP00000360885.4 |
Frequencies
GnomAD3 genomes 0.0000461 AC: 7AN: 151970Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000374 AC: 9AN: 240926Hom.: 0 AF XY: 0.0000455 AC XY: 6AN XY: 131968
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GnomAD4 exome AF: 0.0000583 AC: 85AN: 1459038Hom.: 0 Cov.: 33 AF XY: 0.0000648 AC XY: 47AN XY: 725740
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GnomAD4 genome 0.0000461 AC: 7AN: 151970Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74242
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Feb 20, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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, classic type, 1 Benign:1
Nov 09, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at