rs145608939
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000088.4(COL1A1):c.3123C>T(p.Pro1041=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000724 in 1,612,662 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00076 ( 2 hom. )
Consequence
COL1A1
NM_000088.4 synonymous
NM_000088.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.964
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 17-50188614-G-A is Benign according to our data. Variant chr17-50188614-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 197476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50188614-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.964 with no splicing effect.
BS2
?
High AC in GnomAd4 at 62 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.3123C>T | p.Pro1041= | synonymous_variant | 43/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.2925C>T | p.Pro975= | synonymous_variant | 40/48 | ||
COL1A1 | XM_005257058.5 | c.2853C>T | p.Pro951= | synonymous_variant | 41/49 | ||
COL1A1 | XM_005257059.5 | c.2205C>T | p.Pro735= | synonymous_variant | 30/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.3123C>T | p.Pro1041= | synonymous_variant | 43/51 | 1 | NM_000088.4 | P1 | |
COL1A1 | ENST00000511732.1 | n.67C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000417 AC: 63AN: 150988Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000635 AC: 159AN: 250274Hom.: 1 AF XY: 0.000575 AC XY: 78AN XY: 135552
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GnomAD4 exome AF: 0.000756 AC: 1105AN: 1461550Hom.: 2 Cov.: 34 AF XY: 0.000737 AC XY: 536AN XY: 727078
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GnomAD4 genome ? AF: 0.000410 AC: 62AN: 151112Hom.: 0 Cov.: 32 AF XY: 0.000393 AC XY: 29AN XY: 73876
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 18, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 14, 2016 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 08, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | COL1A1: BP4, BP7, BS1 - |
Ehlers-Danlos syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jun 06, 2022 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2020 | This alteration is classified as likely 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 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at