15-58499155-T-C

Variant names:

• chr15-58499155-T-C
• rs1973028
• NM_000236.3:c.89-39178T>C

Variant summary

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

The NM_000236.3(LIPC):​c.89-39178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,812 control chromosomes in the GnomAD database, including 11,652 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 0.39 (11652 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 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.89-39178T>C		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.89-39178T>C		intron	N/A	ENSP00000299022.5
	LIPC	ENST00000414170.7	TSL:1	c.89-39178T>C		intron	N/A	ENSP00000395569.3
	LIPC	ENST00000559845.5	TSL:1	n.131-42630T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59180 AN: 151696 Hom.: 11628 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.390 AC: 59248 AN: 151812 Hom.: 11652 Cov.: 32 AF XY: 0.390 AC XY: 28947 AN XY: 74188

African (AFR) AF: 0.405 AC: 16749 AN: 41390

American (AMR) AF: 0.496 AC: 7572 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1135 AN: 3460

East Asian (EAS) AF: 0.533 AC: 2733 AN: 5132

South Asian (SAS) AF: 0.387 AC: 1865 AN: 4816

European-Finnish (FIN) AF: 0.318 AC: 3360 AN: 10556

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24510 AN: 67884

Other (OTH) AF: 0.404 AC: 853 AN: 2110

Alfa AF: 0.376 Hom.: 29792

Bravo AF: 0.407

Asia WGS AF: 0.393 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.28
PhyloP100		-2.4
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: rs1973028; hg19: chr15-58791354; COSMIC: COSV54427531; COSMIC: COSV54427531;