GeneBe

rs138425306

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000088.4(COL1A1):​c.3046-10_3046-5delCTCTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

COL1A1
NM_000088.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Publications

0 publications found
Variant links:
Genes affected
COL1A1 (HGNC:2197): (collagen type I alpha 1 chain) This gene encodes the pro-alpha1 chains of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIA, Ehlers-Danlos syndrome Classical type, Caffey Disease and idiopathic osteoporosis. Reciprocal translocations between chromosomes 17 and 22, where this gene and the gene for platelet-derived growth factor beta are located, are associated with a particular type of skin tumor called dermatofibrosarcoma protuberans, resulting from unregulated expression of the growth factor. Two transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]
COL1A1 Gene-Disease associations (from GenCC):
  • Caffey disease
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen
  • combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1
    Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
  • Ehlers-Danlos syndrome
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
  • Ehlers-Danlos syndrome, arthrochalasia type
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
  • osteogenesis imperfecta type 1
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
  • osteogenesis imperfecta type 2
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
  • osteogenesis imperfecta type 3
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
  • osteogenesis imperfecta type 4
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen
  • Ehlers-Danlos syndrome, classic type, 1
    Inheritance: AD Classification: MODERATE Submitted by: ClinGen
  • Ehlers-Danlos syndrome, classic type
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Ehlers-Danlos/osteogenesis imperfecta syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • high bone mass osteogenesis imperfecta
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL1A1NM_000088.4 linkc.3046-10_3046-5delCTCTCT splice_region_variant, intron_variant Intron 41 of 50 ENST00000225964.10 NP_000079.2 P02452
COL1A1XM_011524341.2 linkc.2848-10_2848-5delCTCTCT splice_region_variant, intron_variant Intron 38 of 47 XP_011522643.1
COL1A1XM_005257058.5 linkc.2776-10_2776-5delCTCTCT splice_region_variant, intron_variant Intron 39 of 48 XP_005257115.2
COL1A1XM_005257059.5 linkc.2128-10_2128-5delCTCTCT splice_region_variant, intron_variant Intron 28 of 37 XP_005257116.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL1A1ENST00000225964.10 linkc.3046-10_3046-5delCTCTCT splice_region_variant, intron_variant Intron 41 of 50 1 NM_000088.4 ENSP00000225964.6 P02452
COL1A1ENST00000486572.1 linkn.-251_-246delCTCTCT upstream_gene_variant 3
COL1A1ENST00000511732.1 linkn.-21_-16delCTCTCT upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1389114
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
691784
African (AFR)
AF:
0.00
AC:
0
AN:
31972
American (AMR)
AF:
0.00
AC:
0
AN:
43072
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24652
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37022
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84468
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50372
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5518
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1054950
Other (OTH)
AF:
0.00
AC:
0
AN:
57088
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.1

Splicing

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

Publications

Other links and lift over

dbSNP: rs138425306; hg19: chr17-48266160; API