1-11966298-A-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000302.4(PLOD1):āc.1632A>Cā(p.Ala544Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 1,606,252 control chromosomes in the GnomAD database, including 5,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. A544A) has been classified as Likely benign.
Frequency
Consequence
NM_000302.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLOD1 | NM_000302.4 | c.1632A>C | p.Ala544Ala | synonymous_variant | 15/19 | ENST00000196061.5 | NP_000293.2 | |
PLOD1 | NM_001316320.2 | c.1773A>C | p.Ala591Ala | synonymous_variant | 16/20 | NP_001303249.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLOD1 | ENST00000196061.5 | c.1632A>C | p.Ala544Ala | synonymous_variant | 15/19 | 1 | NM_000302.4 | ENSP00000196061.4 | ||
PLOD1 | ENST00000470133.1 | n.246A>C | non_coding_transcript_exon_variant | 3/3 | 3 | |||||
PLOD1 | ENST00000491536.5 | n.260A>C | non_coding_transcript_exon_variant | 3/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0581 AC: 8818AN: 151662Hom.: 368 Cov.: 28
GnomAD3 exomes AF: 0.0618 AC: 14818AN: 239912Hom.: 560 AF XY: 0.0631 AC XY: 8197AN XY: 129852
GnomAD4 exome AF: 0.0773 AC: 112463AN: 1454472Hom.: 4726 Cov.: 32 AF XY: 0.0765 AC XY: 55328AN XY: 722928
GnomAD4 genome AF: 0.0581 AC: 8816AN: 151780Hom.: 369 Cov.: 28 AF XY: 0.0571 AC XY: 4234AN XY: 74206
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 05, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 09, 2023 | - - |
Ehlers-Danlos syndrome, kyphoscoliotic type 1 Benign:3
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 27, 2023 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 29, 2015 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at