chr17-50189433-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM1PP2BP4_ModerateBS2
The NM_000088.4(COL1A1):āc.2773C>Gā(p.Pro925Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,612,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 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. P925S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000088.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.2773C>G | p.Pro925Ala | missense_variant | 39/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.2575C>G | p.Pro859Ala | missense_variant | 36/48 | ||
COL1A1 | XM_005257059.5 | c.1855C>G | p.Pro619Ala | missense_variant | 26/38 | ||
COL1A1 | XM_005257058.5 | c.2667+246C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.2773C>G | p.Pro925Ala | missense_variant | 39/51 | 1 | NM_000088.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000463 AC: 7AN: 151098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000400 AC: 10AN: 250238Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135440
GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461730Hom.: 0 Cov.: 39 AF XY: 0.0000495 AC XY: 36AN XY: 727168
GnomAD4 genome AF: 0.0000463 AC: 7AN: 151098Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2AN XY: 73840
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 21, 2020 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (Stenson et al., 2014) - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 20, 2023 | The COL1A1 c.2773C>G; p.Pro925Ala variant (rs772929903), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1001743). This variant is observed in the general population with an overall allele frequency of 0.004% (11/281404 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.271). Due to limited information, the clinical significance of this variant is uncertain at this time. - |
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 21, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Osteogenesis imperfecta type I Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at