15-58526584-G-A

Variant names:

• chr15-58526584-G-A
• rs9652472
• NM_000236.3:c.89-11749G>A

Variant summary

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

The NM_000236.3(LIPC):​c.89-11749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,188 control chromosomes in the GnomAD database, including 48,856 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 0.76 (48856 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.89-11749G>A		intron	N/A	NP_000227.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.89-11749G>A		intron	N/A	ENSP00000299022.5
	LIPC	ENST00000414170.7	TSL:1	c.89-11749G>A		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000559845.5	TSL:1	n.131-15201G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116386 AN: 152070 Hom.: 48853 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.765 AC: 116401 AN: 152188 Hom.: 48856 Cov.: 32 AF XY: 0.762 AC XY: 56695 AN XY: 74400

African (AFR) AF: 0.397 AC: 16473 AN: 41460

American (AMR) AF: 0.849 AC: 12990 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3147 AN: 3472

East Asian (EAS) AF: 0.661 AC: 3411 AN: 5160

South Asian (SAS) AF: 0.798 AC: 3848 AN: 4824

European-Finnish (FIN) AF: 0.842 AC: 8935 AN: 10608

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.952 AC: 64739 AN: 68034

Other (OTH) AF: 0.811 AC: 1716 AN: 2116

Alfa AF: 0.891 Hom.: 169464

Bravo AF: 0.748

Asia WGS AF: 0.701 AC: 2437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.73
PhyloP100		0.52
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: rs9652472; hg19: chr15-58818783;