rs8028759

Variant names:

• chr15-58520000-C-T
• rs8028759
• NM_000236.3:c.89-18333C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000236.3(LIPC):​c.89-18333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,778 control chromosomes in the GnomAD database, including 30,595 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30595 hom., cov: 31)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 13 publications found

Genes affected

LIPC (HGNC:6619): (lipase C, hepatic type) Enables phospholipase A1 activity and triglyceride lipase activity. Involved in several processes, including lipid homeostasis; plasma lipoprotein particle remodeling; and triglyceride catabolic process. Located in extracellular space. Implicated in several diseases, including Alzheimer's disease; coronary artery disease; familial combined hyperlipidemia; peripheral vascular disease; and type 2 diabetes mellitus. Biomarker of hyperinsulinism; obesity; and type 1 diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

LIPC Gene-Disease associations (from GenCC):

• hyperlipidemia due to hepatic triglyceride lipase deficiency

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.89-18333C>T		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.89-18333C>T		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95931 AN: 151660 Hom.: 30567 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.630

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.633 AC: 96020 AN: 151778 Hom.: 30595 Cov.: 31 AF XY: 0.628 AC XY: 46544 AN XY: 74156

African (AFR) AF: 0.574 AC: 23730 AN: 41306

American (AMR) AF: 0.654 AC: 9976 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2201 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3103 AN: 5160

South Asian (SAS) AF: 0.597 AC: 2863 AN: 4792

European-Finnish (FIN) AF: 0.578 AC: 6082 AN: 10526

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45876 AN: 67948

Other (OTH) AF: 0.628 AC: 1327 AN: 2112

Alfa AF: 0.662 Hom.: 78897

Bravo AF: 0.635

Asia WGS AF: 0.615 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		-0.015
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8028759; hg19: chr15-58812199;