chr17-50188799-C-CAGAGAG
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_000088.4(COL1A1):c.3046-10_3046-5dupCTCTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Consequence
COL1A1
NM_000088.4 splice_region, intron
NM_000088.4 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.14
Publications
6 publications found
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 diseaseInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen
- combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
- Ehlers-Danlos syndromeInheritance: AD Classification: DEFINITIVE Submitted by: G2P
- Ehlers-Danlos syndrome, arthrochalasia typeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
- osteogenesis imperfecta type 1Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- osteogenesis imperfecta type 2Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- osteogenesis imperfecta type 3Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
- osteogenesis imperfecta type 4Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen
- Ehlers-Danlos syndrome, classic type, 1Inheritance: AD Classification: MODERATE Submitted by: ClinGen
- Ehlers-Danlos syndrome, classic typeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Ehlers-Danlos/osteogenesis imperfecta syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- high bone mass osteogenesis imperfectaInheritance: 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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 17-50188799-C-CAGAGAG is Benign according to our data. Variant chr17-50188799-C-CAGAGAG is described in ClinVar as Likely_benign. ClinVar VariationId is 3712677.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| COL1A1 | NM_000088.4 | c.3046-10_3046-5dupCTCTCT | splice_region_variant, intron_variant | Intron 41 of 50 | ENST00000225964.10 | NP_000079.2 | ||
| COL1A1 | XM_011524341.2 | c.2848-10_2848-5dupCTCTCT | splice_region_variant, intron_variant | Intron 38 of 47 | XP_011522643.1 | |||
| COL1A1 | XM_005257058.5 | c.2776-10_2776-5dupCTCTCT | splice_region_variant, intron_variant | Intron 39 of 48 | XP_005257115.2 | |||
| COL1A1 | XM_005257059.5 | c.2128-10_2128-5dupCTCTCT | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| COL1A1 | ENST00000225964.10 | c.3046-5_3046-4insCTCTCT | splice_region_variant, intron_variant | Intron 41 of 50 | 1 | NM_000088.4 | ENSP00000225964.6 | |||
| COL1A1 | ENST00000486572.1 | n.-246_-245insCTCTCT | upstream_gene_variant | 3 | ||||||
| COL1A1 | ENST00000511732.1 | n.-16_-15insCTCTCT | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.20e-7 AC: 1AN: 1389182Hom.: 0 Cov.: 0 AF XY: 0.00000145 AC XY: 1AN XY: 691826 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1389182
Hom.:
Cov.:
0
AF XY:
AC XY:
1
AN XY:
691826
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31970
American (AMR)
AF:
AC:
0
AN:
43072
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24652
East Asian (EAS)
AF:
AC:
0
AN:
37022
South Asian (SAS)
AF:
AC:
0
AN:
84468
European-Finnish (FIN)
AF:
AC:
0
AN:
50374
Middle Eastern (MID)
AF:
AC:
0
AN:
5518
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1055018
Other (OTH)
AF:
AC:
0
AN:
57088
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Osteogenesis imperfecta type I Benign:1
Nov 22, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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