rs754984293
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_000088.4(COL1A1):c.3994G>A(p.Asp1332Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1332G) has been classified as Likely benign.
Frequency
Consequence
NM_000088.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.3994G>A | p.Asp1332Asn | missense_variant | 49/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.3796G>A | p.Asp1266Asn | missense_variant | 46/48 | ||
COL1A1 | XM_005257058.5 | c.3724G>A | p.Asp1242Asn | missense_variant | 47/49 | ||
COL1A1 | XM_005257059.5 | c.3076G>A | p.Asp1026Asn | missense_variant | 36/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.3994G>A | p.Asp1332Asn | missense_variant | 49/51 | 1 | NM_000088.4 | P1 | |
COL1A1 | ENST00000510710.3 | n.663G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251384Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135882
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461850Hom.: 0 Cov.: 34 AF XY: 0.0000220 AC XY: 16AN XY: 727234
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74392
ClinVar
Submissions by phenotype
Infantile cortical hyperostosis;C0023931:Osteogenesis imperfecta type I;C0029458:Postmenopausal osteoporosis;C0268335:Ehlers-Danlos syndrome, classic type, 1;C0268358:Osteogenesis imperfecta, perinatal lethal;C0268362:Osteogenesis imperfecta type III;C0268363:Osteogenesis imperfecta with normal sclerae, dominant form;C4551623:Ehlers-Danlos syndrome, arthrochalasia type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Oct 21, 2021 | COL1A1 NM_000088.3 exon 49 p.Asp1332Asn (c.3994G>A):This variant has not been reported in the literature but is present in 0.002% (2/68046) of European alleles in the Genome Aggregation Database (hhttps://gnomad.broadinstitute.org/variant/17-50186328-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:578894). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 27, 2021 | The p.D1332N variant (also known as c.3994G>A), located in coding exon 49 of the COL1A1 gene, results from a G to A substitution at nucleotide position 3994. The aspartic acid at codon 1332 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Osteogenesis imperfecta type I Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at