rs59184895
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000237.3(LPL):c.1018+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,613,982 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 44 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 50 hom. )
Consequence
LPL
NM_000237.3 intron
NM_000237.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.644
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 8-19956099-T-C is Benign according to our data. Variant chr8-19956099-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 495740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19956099-T-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1942/152300) while in subpopulation AFR AF= 0.0446 (1853/41552). AF 95% confidence interval is 0.0429. There are 44 homozygotes in gnomad4. There are 893 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 44 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LPL | NM_000237.3 | c.1018+16T>C | intron_variant | ENST00000650287.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LPL | ENST00000650287.1 | c.1018+16T>C | intron_variant | NM_000237.3 | P1 | ||||
LPL | ENST00000650478.1 | c.79+16T>C | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0127 AC: 1932AN: 152182Hom.: 44 Cov.: 33
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GnomAD3 exomes AF: 0.00346 AC: 869AN: 251006Hom.: 23 AF XY: 0.00264 AC XY: 358AN XY: 135718
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GnomAD4 exome AF: 0.00136 AC: 1994AN: 1461682Hom.: 50 Cov.: 32 AF XY: 0.00116 AC XY: 846AN XY: 727162
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GnomAD4 genome ? AF: 0.0128 AC: 1942AN: 152300Hom.: 44 Cov.: 33 AF XY: 0.0120 AC XY: 893AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 08, 2017 | Variant summary: The LPL c.1018+16T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 515/121272 control chromosomes (17 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.046758 (486/10394). This frequency is about 14 times the estimated maximal expected allele frequency of a pathogenic LPL variant (0.0033541), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2019 | - - |
Computational scores
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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