rs75389218
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001349206.2(LPIN1):c.2162+39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,601,656 control chromosomes in the GnomAD database, including 66 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 ( 32 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 34 hom. )
Consequence
LPIN1
NM_001349206.2 intron
NM_001349206.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.52
Genes affected
LPIN1 (HGNC:13345): (lipin 1) This gene encodes a magnesium-ion-dependent phosphatidic acid phosphohydrolase enzyme that catalyzes the penultimate step in triglyceride synthesis including the dephosphorylation of phosphatidic acid to yield diacylglycerol. Expression of this gene is required for adipocyte differentiation and it also functions as a nuclear transcriptional coactivator with some peroxisome proliferator-activated receptors to modulate expression of other genes involved in lipid metabolism. Mutations in this gene are associated with metabolic syndrome, type 2 diabetes, acute recurrent rhabdomyolysis, and autosomal recessive acute recurrent myoglobinuria (ARARM). This gene is also a candidate for several human lipodystrophy syndromes. [provided by RefSeq, Mar 2017]
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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=-0.82).
BP6
Variant 2-11804610-T-C is Benign according to our data. Variant chr2-11804610-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 262590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (1896/142482) while in subpopulation AFR AF= 0.0501 (1794/35842). AF 95% confidence interval is 0.0481. There are 32 homozygotes in gnomad4. There are 870 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 32 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LPIN1 | NM_001349206.2 | c.2162+39T>C | intron_variant | ENST00000674199.1 | NP_001336135.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LPIN1 | ENST00000674199.1 | c.2162+39T>C | intron_variant | NM_001349206.2 | ENSP00000501331 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0133 AC: 1895AN: 142386Hom.: 32 Cov.: 32
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GnomAD3 exomes AF: 0.00318 AC: 794AN: 249574Hom.: 16 AF XY: 0.00242 AC XY: 327AN XY: 135072
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GnomAD4 exome AF: 0.00134 AC: 1950AN: 1459174Hom.: 34 Cov.: 30 AF XY: 0.00113 AC XY: 823AN XY: 726042
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GnomAD4 genome AF: 0.0133 AC: 1896AN: 142482Hom.: 32 Cov.: 32 AF XY: 0.0125 AC XY: 870AN XY: 69786
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 10, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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