rs316
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000237.3(LPL):c.1164C>A(p.Thr388=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,612,340 control chromosomes in the GnomAD database, including 14,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.16 ( 2009 hom., cov: 31)
Exomes 𝑓: 0.13 ( 12298 hom. )
Consequence
LPL
NM_000237.3 synonymous
NM_000237.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.57
Genes affected
LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 8-19960925-C-A is Benign according to our data. Variant chr8-19960925-C-A is described in ClinVar as [Benign]. Clinvar id is 362413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19960925-C-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.57 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LPL | NM_000237.3 | c.1164C>A | p.Thr388= | synonymous_variant | 8/10 | ENST00000650287.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LPL | ENST00000650287.1 | c.1164C>A | p.Thr388= | synonymous_variant | 8/10 | NM_000237.3 | P1 | ||
LPL | ENST00000650478.1 | c.104C>A | p.Pro35His | missense_variant, NMD_transcript_variant | 2/4 |
Frequencies
GnomAD3 genomes ? AF: 0.155 AC: 23541AN: 151804Hom.: 2000 Cov.: 31
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GnomAD3 exomes AF: 0.135 AC: 33843AN: 251348Hom.: 2482 AF XY: 0.133 AC XY: 18048AN XY: 135840
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GnomAD4 exome AF: 0.127 AC: 185694AN: 1460422Hom.: 12298 Cov.: 33 AF XY: 0.127 AC XY: 92390AN XY: 726602
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GnomAD4 genome ? AF: 0.155 AC: 23575AN: 151918Hom.: 2009 Cov.: 31 AF XY: 0.154 AC XY: 11435AN XY: 74254
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hyperlipoproteinemia, type I Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 20, 2019 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 09, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2018 | 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. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at