rs1555573640
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_000088.4(COL1A1):āc.1689T>Cā(p.Gly563=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 31)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
COL1A1
NM_000088.4 synonymous
NM_000088.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0600
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 Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant 17-50194021-A-G is Benign according to our data. Variant chr17-50194021-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 456738.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.06 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.1689T>C | p.Gly563= | synonymous_variant | 25/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.1491T>C | p.Gly497= | synonymous_variant | 22/48 | ||
COL1A1 | XM_005257058.5 | c.1689T>C | p.Gly563= | synonymous_variant | 25/49 | ||
COL1A1 | XM_005257059.5 | c.958-1328T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.1689T>C | p.Gly563= | synonymous_variant | 25/51 | 1 | NM_000088.4 | P1 | |
COL1A1 | ENST00000463440.1 | n.79T>C | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
COL1A1 | ENST00000471344.1 | n.721T>C | non_coding_transcript_exon_variant | 8/8 | 2 | ||||
COL1A1 | ENST00000476387.1 | n.38T>C | non_coding_transcript_exon_variant | 1/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151918Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461774Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727186
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151918Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74174
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Osteogenesis imperfecta type I Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 19, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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