rs112250644
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_000302.4(PLOD1):c.1582G>A(p.Glu528Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000173 in 1,598,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000302.4 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLOD1 | NM_000302.4 | c.1582G>A | p.Glu528Lys | missense_variant, splice_region_variant | 14/19 | ENST00000196061.5 | |
PLOD1 | NM_001316320.2 | c.1723G>A | p.Glu575Lys | missense_variant, splice_region_variant | 15/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLOD1 | ENST00000196061.5 | c.1582G>A | p.Glu528Lys | missense_variant, splice_region_variant | 14/19 | 1 | NM_000302.4 | P1 | |
PLOD1 | ENST00000470133.1 | n.196G>A | splice_region_variant, non_coding_transcript_exon_variant | 2/3 | 3 | ||||
PLOD1 | ENST00000491536.5 | n.210G>A | splice_region_variant, non_coding_transcript_exon_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000775 AC: 118AN: 152186Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000295 AC: 74AN: 250438Hom.: 0 AF XY: 0.000251 AC XY: 34AN XY: 135528
GnomAD4 exome AF: 0.000109 AC: 158AN: 1445848Hom.: 0 Cov.: 28 AF XY: 0.000101 AC XY: 73AN XY: 720288
GnomAD4 genome ? AF: 0.000775 AC: 118AN: 152304Hom.: 0 Cov.: 31 AF XY: 0.000685 AC XY: 51AN XY: 74474
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 18, 2022 | BS1 - |
Ehlers-Danlos syndrome, kyphoscoliotic type 1 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 29, 2021 | The PLOD1 c.1582G>A; p.Glu528Lys variant (rs112250644), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 459811). This variant is found in the African/African-American population with an allele frequency of 0.27% (68/24928 alleles) in the Genome Aggregation Database. The glutamate at codon 528 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.537). Due to limited information, the clinical significance of the p.Glu528Lys variant is uncertain at this time. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 24, 2023 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 10, 2017 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at