rs41316673
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000088.4(COL1A1):c.2115C>T(p.Asn705=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,587,696 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00027 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
COL1A1
NM_000088.4 synonymous
NM_000088.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.52
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 17-50191800-G-A is Benign according to our data. Variant chr17-50191800-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 456743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50191800-G-A is described in Lovd as [Likely_benign]. Variant chr17-50191800-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.52 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000155 (223/1435446) while in subpopulation AMR AF= 0.00341 (140/41012). AF 95% confidence interval is 0.00295. There are 0 homozygotes in gnomad4_exome. There are 100 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.2115C>T | p.Asn705= | synonymous_variant | 31/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.1917C>T | p.Asn639= | synonymous_variant | 28/48 | ||
COL1A1 | XM_005257058.5 | c.2115C>T | p.Asn705= | synonymous_variant | 31/49 | ||
COL1A1 | XM_005257059.5 | c.1197C>T | p.Asn399= | synonymous_variant | 18/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.2115C>T | p.Asn705= | synonymous_variant | 31/51 | 1 | NM_000088.4 | P1 | |
COL1A1 | ENST00000476387.1 | n.464C>T | non_coding_transcript_exon_variant | 7/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152132Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000652 AC: 136AN: 208682Hom.: 0 AF XY: 0.000507 AC XY: 57AN XY: 112316
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GnomAD4 exome AF: 0.000155 AC: 223AN: 1435446Hom.: 0 Cov.: 33 AF XY: 0.000141 AC XY: 100AN XY: 711628
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GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152250Hom.: 1 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74456
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 23, 2023 | - - |
Osteogenesis imperfecta Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 23, 2022 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 18, 2022 | This alteration is classified as 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. - |
Osteogenesis imperfecta type I Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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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