GeneBe

9-134785950-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000093.5(COL5A1):​c.2593-45G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131

Publications

5 publications found
Variant links:
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]
COL5A1 Gene-Disease associations (from GenCC):
  • Ehlers-Danlos syndrome
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
  • Ehlers-Danlos syndrome, classic type
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
  • Ehlers-Danlos syndrome, classic type, 1
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • arterial disorder
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL5A1NM_000093.5 linkc.2593-45G>C intron_variant Intron 30 of 65 ENST00000371817.8 NP_000084.3 P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1NM_001278074.1 linkc.2593-45G>C intron_variant Intron 30 of 65 NP_001265003.1 B2ZZ86Q59EE7
COL5A1XM_017014266.3 linkc.2593-45G>C intron_variant Intron 30 of 64 XP_016869755.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL5A1ENST00000371817.8 linkc.2593-45G>C intron_variant Intron 30 of 65 1 NM_000093.5 ENSP00000360882.3 P20908-1
COL5A1ENST00000371820.4 linkc.2593-45G>C intron_variant Intron 30 of 65 2 ENSP00000360885.4 P20908-2H7BY82

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.12e-7
AC:
1
AN:
1404070
Hom.:
0
Cov.:
25
AF XY:
0.00000143
AC XY:
1
AN XY:
701508
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32312
American (AMR)
AF:
0.00
AC:
0
AN:
44032
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25708
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39224
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83936
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52676
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5690
European-Non Finnish (NFE)
AF:
9.42e-7
AC:
1
AN:
1061946
Other (OTH)
AF:
0.00
AC:
0
AN:
58546
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.28
DANN
Benign
0.70
PhyloP100
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs45497895; hg19: chr9-137677796; API