rs2586488
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000088.4(COL1A1):c.3261+31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,612,540 control chromosomes in the GnomAD database, including 376,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.66 ( 33444 hom., cov: 33)
Exomes 𝑓: 0.68 ( 343528 hom. )
Consequence
COL1A1
NM_000088.4 intron
NM_000088.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.761
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]
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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=-0.84).
BP6
?
Variant 17-50188065-A-G is Benign according to our data. Variant chr17-50188065-A-G is described in ClinVar as [Benign]. Clinvar id is 674808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.3261+31T>C | intron_variant | ENST00000225964.10 | |||
COL1A1 | XM_005257058.5 | c.2991+31T>C | intron_variant | ||||
COL1A1 | XM_005257059.5 | c.2343+31T>C | intron_variant | ||||
COL1A1 | XM_011524341.2 | c.3063+31T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.3261+31T>C | intron_variant | 1 | NM_000088.4 | P1 | |||
COL1A1 | ENST00000511732.1 | n.616T>C | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
COL1A1 | ENST00000486572.1 | n.459+31T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.660 AC: 100302AN: 152006Hom.: 33421 Cov.: 33
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GnomAD3 exomes AF: 0.670 AC: 166345AN: 248426Hom.: 56155 AF XY: 0.668 AC XY: 89834AN XY: 134404
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GnomAD4 exome AF: 0.684 AC: 999503AN: 1460416Hom.: 343528 Cov.: 43 AF XY: 0.681 AC XY: 494916AN XY: 726378
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GnomAD4 genome ? AF: 0.660 AC: 100370AN: 152124Hom.: 33444 Cov.: 33 AF XY: 0.660 AC XY: 49082AN XY: 74356
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Osteogenesis imperfecta type III Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Ehlers-Danlos syndrome, arthrochalasia type Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Osteogenesis imperfecta with normal sclerae, dominant form Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
Osteogenesis imperfecta, perinatal lethal Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Osteogenesis imperfecta type I Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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