chr1-11934716-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000449038.5(PLOD1):c.-64C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,505,918 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )
Consequence
PLOD1
ENST00000449038.5 5_prime_UTR
ENST00000449038.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.237
Genes affected
PLOD1 (HGNC:9081): (procollagen-lysine,2-oxoglutarate 5-dioxygenase 1) Lysyl hydroxylase is a membrane-bound homodimeric protein localized to the cisternae of the endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VI have deficiencies in lysyl hydroxylase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLOD1 | NM_000302.4 | upstream_gene_variant | ENST00000196061.5 | ||||
PLOD1 | NM_001316320.2 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLOD1 | ENST00000196061.5 | upstream_gene_variant | 1 | NM_000302.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152204Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000495 AC: 67AN: 1353714Hom.: 0 Cov.: 31 AF XY: 0.0000434 AC XY: 29AN XY: 667732
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74346
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, kyphoscoliotic type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at